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Simple Summary: Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite multiple standardized interpretation criteria (SICs) for imaging response assessment in patients with head and neck squamous cell carcinoma (HNSCC), these systems remain relatively underutilized. This underutilization may in part relate to the fact that the relevant information has been published in disparate journals over multiple decades. This paper aims to review the SICs available for use in interpreting post-treatment FDG PET/CT in patients with HNSCC. We evaluate each SIC in the context of eight desired traits. Selecting a SIC that best matches the needs of one's practice is expected to facilitate multidisciplinary buy-in and maximize the likelihood of successful implementation. Introduction: There is growing interest in the development and application of standardized imaging criteria (SIC), to minimize variability and improve the reproducibility of image interpretation in head and neck squamous cell carcinoma (HNSCC). Methods: "Squamous cell carcinoma" AND "standardized interpretation criteria" OR "radiographic response assessment" were searched using PubMed and Google Scholar for articles published between 2009 and 2024, returning 56 publications. After abstract review, 18 were selected for further evaluation, and 6 different SICs (i.e., PERCIST, Porceddu, Hopkins, NI-RADS, modified Deauville, and Cuneo) were included in this review. Each SIC is evaluated in the context of 8 desired traits of a standardized reporting system. Results: Two SICs have societal endorsements (i.e., PERCIST, NI-RADS); four can be used in the evaluation of locoregional and systemic disease (i.e., PERCIST, Hopkins, NI-RADS, Cuneo), and four have specific categories for equivocal imaging results (i.e., Porceddu, NI-RADS, modified Deauville, and Cuneo). All demonstrated areas for future improvement in the context of the 8 desired traits. Conclusion: Multiple SICs have been developed for and demonstrated value in HNSCC post-treatment imaging; however, these systems remain underutilized. Selecting an SIC with features that best match the needs of one's practice is expected to maximize the likelihood of successful implementation. [ABSTRACT FROM AUTHOR]

Simple Summary: Among head–neck tumors, squamous cell carcinoma is the most frequent histotype and includes a range of malignancies with different sites of origin as well as different therapeutic strategies and clinical outcomes. In daily practice, patients with head–neck squamous cell carcinoma are seen in various clinical settings, requiring a multidisciplinary approach to therapeutic decisions and clinical care. 18F-FDG PET/CT plays a well-defined role in the management of these tumors for pre-treatment staging and radiotherapy planning as well as treatment-response assessment and post-therapy follow-up. This paper is an overview of the standard use of 18F-FDG PET/CT in the various clinical scenarios of head–neck squamous cell carcinoma. Also, emerging applications will be reviewed, including the use of radiopharmaceuticals other than 18F-FDG, PET/MRI implementation in clinical practice, and the use of radiomics and machine learning. This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs. [ABSTRACT FROM AUTHOR]

Simple Summary: This article summarises the international Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial for patients with rhabdomyosarcoma. The trial has multiple research questions relating to chemotherapy and radiotherapy and biological and imaging studies as well as to the introduction of novel drugs for patients with very high-risk disease. The rationale, background, and international collaboration of the trial are explained, and how the data will be used to inform future studies is outlined. The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results. [ABSTRACT FROM AUTHOR]

Simple Summary: Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals is a relatively novel technique currently employed in the management of prostate cancer patients. These radiopharmaceuticals target PSMA, also known as carboxypeptidase type II, which is mainly expressed by prostate cancer cells. Nevertheless, its expression has been observed in the neovasculature of various kinds of cancer, including clear cell renal cell carcinoma (ccRCC). Based on this biological mechanism, several authors postulated a potential role for this diagnostic method in ccRCC patients in different clinical settings. This systematic review provides an overview of the possible applications of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Background: Recent articles proposed the employment of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in clear cell renal cell carcinoma (ccRCC). Methods: The authors performed a comprehensive literature search of studies on the performance of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Original articles concerning this imaging examination were included in newly diagnosed ccRCC patients and ccRCC patients with disease recurrence. Results: A total of sixteen papers concerning the diagnostic performance of PSMA-targeted PET/CT in ccRCC (331 patients) were included in this systematic review. The included articles demonstrated an excellent detection rate of PSMA-targeting PET/CT in ccRCC. Conclusions: PSMA-targeted PET/CT seems promising in detecting ccRCC lesions as well as in discriminating the presence of aggressive phenotypes. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting PET/CT in ccRCC. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper aims to improve the knowledge regarding 18F-FDOPA PET/CT parameters that may influence both the interpretation of PET data and the management of primary brain tumors. The evaluation of volumetric parameters in 18F-FDOPA imaging is uncommon, and we aim to increase the scientific interest on the potential role of volumetric parameters in the clinical practice. The standardized uptake value (SUV)-derived indices as SUV max, SUV mean, SUV max ratio, and SUV mean ratio are widely used but the exact methodology to elaborate SUV ratio is not well established. Therefore, this study aims to assess the correlation between SUV-derived indices and volumetric uptake parameters. Novel parameters in PET imaging, such as volumetric parameters, are gaining interest in the scientific literature, but the role of dopaminergic tumor volume (DTV) and total lesion F-DOPA activity (TLDA) and the correlation between volumetric and SUV-derived parameters are not well defined yet. One hundred and thirty-three patients that underwent 18F-FDOPA imaging for primary brain tumors were included in this retrospective study. SUV-derived indices were calculated (the occipital region was chosen to generate ratios of tumor SUV) and compared with volumetric parameters. Regression models were applied in univariate analysis and lnSUVmax was positively associated with lnDTV (beta 0.42, p = 0.007), the lnSUVmax ratio was positively associated with lnDTV (beta 0.80, p = 0.011), lnSUVmax was positively associated with lnTLDA (beta 1.27, p < 0.0001), and the lnSUVmax ratio was positively associated with lnTLDA (beta 1.87, p < 0.0001). Our study demonstrates that volumetric uptake parameters in 18F-FDOPA PET/CT are easier to assess in primary brain tumors with higher SUV max and SUV max ratios, and supports the emerging role of volumetric parameters in the data interpretation. [ABSTRACT FROM AUTHOR]

Simple Summary: This research explores the role of different methods for assessing bone marrow infiltration (BMI) in mantle cell lymphoma (MCL) during initial diagnosis. Traditional bone marrow biopsy (BMB) is a standard procedure, but newer imaging techniques like PET/CT scans may offer additional or alternative insights. Our study aims to clarify the diagnostic accuracy and prognostic value of these methods, both individually and in combination, for predicting patient outcomes. We propose a new prognostic model that integrates PET/CT results, which could improve the ability to classify patients by risk. The findings may impact clinical approaches by guiding better-informed decisions in MCL diagnosis and prognosis. Background: Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking. Objectives: To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB in a large series of MCL patients. Methods: We deconstructed the IPI-NCCN, MIPI, and MIPI-c indices and considered BMI as positive if indicated by a BMB, PET/CT scan, or a combination of both. Results: In the total cohort (n = 148), 110 patients had BMI detected by BMB and 33 by PET/CT. The sensitivity of BMB was higher than that of PET/CT (94.8% vs. 28.4%), as were its negative predictive value (84.2% vs. 27.8%) and accuracy (95.9% vs. 43.9%). In the total cohort, BMI detected by PET/CT showed a significant predictive value for PFS (p = 0.027), while BMB demonstrated independent prognostic value only in combination with PET/CT (p = 0.025). Among intensively treated patients (n = 128), PET/CT had significant clinical impact on PFS (p = 0.030), and when combined with BMB, it provided independent prognostic value for both PFS and OS (p = 0.026 and p = 0.033, respectively). Based on these findings, we propose a prognostic model (MCL-PET-I) that incorporates BMI by PET/CT, allowing for the identification of three groups with distinct clinical outcomes (p < 0.0001 for PFS and p = 0.00025 for OS). Conclusions: In the upfront work of MCL, PET/CT-based BMI has greater prognostic impact, while BMB remains essential for staging. We propose the MCL-PET-I prognostic index, which effectively differentiates between clinical risk groups. [ABSTRACT FROM AUTHOR]

Simple Summary: Locally advanced cervical cancer (LACC) poses a significant challenge in oncology due to its heterogeneous nature and inconsistent response to standard chemoradiation therapy. The ability to predict response to treatment early in LACC has profound implications for enhancing patient care through tailored and adaptive therapies. Sequential FDG-PET imaging is crucial in managing LACC, offering a non-invasive method to assess tumor progression and response to chemoradiation over the course of treatment. The current study had recourse to longitudinal FDG-PET radiomics for early prediction of treatment response to chemoradiation in LACC. The implications of this study aid in demonstrating the potentially pivotal role of longitudinal radiomics in personalized medicine and improving therapeutic outcomes for LACC. Objectives: This study aimed to assess the capacity of longitudinal FDG-PET radiomics for early distinguishing between locally advanced cervical cancer (LACC) patients who responded to treatment and those who did not. Methods: FDG-PET scans were obtained before and midway through concurrent chemoradiation for a study cohort of patients with LACC. Radiomics features related to image textures were extracted from the primary tumor volumes and stratified for relevance to treatment response status with the aid of random forest recursive feature elimination. Predictive models based on the k-nearest neighbors time series classifier were developed using the top-selected features to differentiate between responders and non-responders. The performance of the developed models was evaluated using receiver operating characteristic (ROC) curve analysis and n-fold cross-validation. Results: The top radiomics features extracted from scans taken midway through treatment showed significant differences between the two responder groups (p-values < 0.0005). In contrast, those from pretreatment scans did not exhibit significant differences. The AUC of the mean ROC curve for the predictive model based on the top features from pretreatment scans was 0.8529, while it reached 0.9420 for those derived midway through treatment scans. Conclusions: The study highlights the potential of longitudinal FDG-PET radiomics extracted midway through treatment for predicting response to chemoradiation in LACC patients and emphasizes that interim PET scans could be crucial in personalized medicine, ultimately enhancing therapeutic outcomes for LACC. [ABSTRACT FROM AUTHOR]

Simple Summary: The most frequent initial site of metastasis for patients with melanoma is the regional lymph node basin. Management of regional lymph nodes was transformed through the development of lymphatic mapping and sentinel lymph node biopsy. Through a series of prospective multicenter clinical trials, the role of sentinel lymph node biopsy has been established and clarified. Although areas of controversy remain, the procedure now has a well-defined role in treatment and holds promise as a source of valuable information to guide our understanding of melanoma biology and treatment into the future. Starting with its earliest descriptions, melanoma has been recognized as a tumor with a predilection for metastasis to regional lymph nodes. This tendency led to initial recommendations for very aggressive early surgical management of the regional nodal basin. However, those recommendations were the source of much controversy over nearly a century, until the minimally invasive surgical technique of sentinel lymph node (SLN) biopsy was developed by Morton, Cochran and colleagues. This technique has been evaluated in a series of prospective clinical trials, which have clarified its role and the management of lymph nodes in this disease. Current controversies relating to SLN biopsy include optimal selection of patients for the procedure, the role of gene expression profiling in initial melanoma management, and the potential therapeutic effects of SLN biopsy-based management. In addition, the SLN appears to be a rich source of data relating to the host–tumor interface and the immune microenvironment, which may advance our understanding of the biology of melanoma. Finally, although the surgical technique is well developed at this point, there may be additional technical improvements that are possible as well. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphoma is a type of cancer that affects the immune system and can be difficult to diagnose and treat effectively, especially in the early stages. Current imaging methods, such as PET/CT scans, are valuable tools for diagnosing and monitoring the disease, but they have limitations in providing precise information for personalized treatment plans. Recently, radiomics and artificial intelligence (AI) have emerged as promising technologies that can analyze detailed patterns in medical images, helping to uncover information that might not be visible to the human eye. This study explores the potential of these technologies in improving the diagnosis, staging, and treatment selection for lymphoma patients. However, further research is needed to confirm their reliability and ensure they can be effectively used in clinical practice. Lymphoma, encompassing a wide spectrum of immune system malignancies, presents significant complexities in its early detection, management, and prognosis assessment since it can mimic post-infectious/inflammatory diseases. The heterogeneous nature of lymphoma makes it challenging to definitively pinpoint valuable biomarkers for predicting tumor biology and selecting the most effective treatment strategies. Although molecular imaging modalities, such as positron emission tomography/computed tomography (PET/CT), specifically 18F-FDG PET/CT, hold significant importance in the diagnosis of lymphoma, prognostication, and assessment of treatment response, they still face significant challenges. Over the past few years, radiomics and artificial intelligence (AI) have surfaced as valuable tools for detecting subtle features within medical images that may not be easily discerned by visual assessment. The rapid expansion of AI and its application in medicine/radiomics is opening up new opportunities in the nuclear medicine field. Radiomics and AI capabilities seem to hold promise across various clinical scenarios related to lymphoma. Nevertheless, the need for more extensive prospective trials is evident to substantiate their reliability and standardize their applications. This review aims to provide a comprehensive perspective on the current literature regarding the application of AI and radiomics applied/extracted on/from 18F-FDG PET/CT in the management of lymphoma patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer remainsa leading cause of cancer-related deaths in men worldwide. This review focuses on the transformative role of prostate-specific membrane antigen (PSMA) in the diagnosis and treatment of prostate cancer. PSMA is highly expressed in prostate cancer cells, making it a valuable target for both imaging and therapy. The integration of PSMA-targeted imaging with radioligand therapy, known as theranostics, has significantly improved the detection and management of advanced prostate cancer. Recent clinical trials, including the VISION trial, have demonstrated the effectiveness of PSMA-targeted therapies, such as 177Lu-PSMA-617. These advancements highlight the potential of theranostics in offering personalized and more effective treatment options for prostate cancer patients. Prostate cancer, a leading cause of cancer-related mortality among men, is characterized by complex genetic and epigenetic alterations, dysregulation of oncogenic pathways, and a dynamic tumor microenvironment. Advances in molecular diagnostics and targeted therapies have significantly transformed the management of this disease. Prostate-specific membrane antigen (PSMA) has emerged as a critical biomarker, enhancing the precision of prostate cancer diagnosis and treatment. Theranostics, which integrates PSMA-targeted imaging with radioligand therapies, has shown remarkable efficacy in detecting and treating advanced prostate cancer. By leveraging the dual capabilities of PSMA-based diagnostics and therapeutic agents, theranostics offers a personalized approach that improves patient outcomes. This comprehensive review explores the latest developments in PSMA-targeted theranostics and their impact on the future of prostate cancer management, highlighting key clinical trials and emerging therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: With the aim of offering precision medicine to our patients, accurate lymph node staging of head and neck (HN) cancer patients is a major challenge, as it determines whether neck dissection is indicated. For many years, the indication for this surgery has been histological predictors from the primary tumor only, and efforts are converging to develop non-invasive techniques to exclude occult metastases with certainty. FDG PET-CT plays a dominant role in this respect. The aim of our systematic review and meta-analysis was to determine the overall diagnostic performance of FDG PET-CT for the detection of LN metastases from HN squamous cell carcinoma (HNSCC) in patients with clinically node-negative necks. Because of an estimated 20–30% prevalence of occult lymph node (LN) metastases in patients with head and neck squamous cell carcinoma (HNSCC), neck dissection is often proposed, despite its potential morbidity. In this systematic review and meta-analysis, the diagnostic performance of FDG PET-CT in detecting occult LN metastases was evaluated in patients with clinically negative necks (cN0) and in whom histopathology of a neck dissection specimen served as gold standard. Overall, 16 studies out of 2062 screened on PubMed and EMBASE fulfilled the inclusion criteria (n = 1148 patients). Seven of these sixteen studies were split into two or three studies because they contained data that could be processed distinctly in our meta-analysis. For this reason, a total of 25 studies were identified and included in the analysis (n total = 1918 patients). The overall prevalence of metastatic nodes per patient was 22.67%. The pooled sensitivity, specificity, diagnostic odds ratios, and negative predictive value (NPV) were 0.71 (95%CI: 0.66–0.75), 0.90 (95%CI: 0.84–0.93), 20.03 (95%CI: 13.51–29.70), and 0.92 (95%CI: 0.89–0.95), respectively. The main causes of inter-study heterogeneity included different reference standards (evaluation per patient, per neck side, or per neck level). The current meta-analysis showed that FDG PET-CT has a high specificity and NPV for ruling out nodal involvement in cN0 necks, but a limited sensitivity. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most prevalent forms of cancer diagnosed in women worldwide. Since the estradiol receptor (ER) is overexpressed in 75% of breast tumors, it is a reasonable target for tumor diagnosis and therapy. This study focuses on the development and preclinical evaluation of readily synthesized 18F-labeled estradiol derivatives with different lipophilicity. The least hydrophilic derivative, 18F-TA-Glyco-EE, showed the highest cellular uptake in ER-positive breast cancer cells. The in vivo PET imaging of breast tumor-bearing mice demonstrated the desired rapid clearance of the tracer from the excretory organ through the liver. The in vitro autoradiography of ER-positive tumor sections confirmed the high specific binding of 18F-TA-Glyco-EE. In conclusion, 18F-TA-Glyco-EE may be a promising candidate for imaging of ER-positive breast cancer. About 75% of breast tumors show an overexpression of the estradiol receptor (ER), making it a valuable target for tumor diagnosis and therapy. To date, 16α-[18F]fluoroestradiol (FES) is the only FDA-approved imaging probe for the positron emission tomography (PET) imaging of ER-positive (ER+) breast cancer. However, FES has the drawback of a high retention in the liver. Therefore, the aim of this study was the development and preclinical evaluation of estradiol (E2) derivatives with different lipophilicity. Three 18F-labeled prosthetic groups (two glycosyl and one PEG azide) were chosen for conjugation with ethinyl estradiol (EE) by 18F-CuAAC (Cu-catalyzed azide-alkyne cycloaddition). The cellular uptake in ER+ MCF-7 tumor cells was highest for the less hydrophilic derivative (18F-TA-Glyco-EE). In nude mice bearing different breast tumors (ER+ MCF-7 and T47D versus ER− MDA-MB-231), 18F-TA-Glyco-EE revealed a high uptake in the liver (13%ID/g, 30 min p.i.), which decreased over 90 min to 1.2%ID/g, indicating fast hepatobiliary clearance. The statistically significant difference of 18F-TA-Glyco-EE uptake in T47D compared to MDA-MB-231 tumors at 60–90 min p.i. indicated ER-specific uptake, whereas in vivo PET imaging did not provide evidence for specific uptake of 18F-TA-Glyco-EE in MCF-7 tumors, probably due to ER occupation by E2 after E2-dependent MCF-7 tumor growth in mice. However, in vitro autoradiography revealed a high specific binding of 18F-TA-Glyco-EE to ER+ tumor slices. We conclude that 18F-TA-Glyco-EE, with its increased hydrophilicity after deacetylation in the blood and thus rapid washout from non-target tissues, may be a viable alternative to FES for the PET imaging of breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma (CCA) is a type of liver cancer with few treatment options and low survival rates in advanced stages. Our study developed a mouse model to study this cancer type by implanting CCA cells into the liver of mice. We used advanced imaging techniques (MRI and PET scans) to monitor tumor growth and metabolism over four weeks. We observed that tumors became visible early and grew steadily over time. PET scans showed increasing tumor activity, and blood tests revealed liver damage. Most mice developed lung metastases after four weeks. Our research shows that combining MRI and PET scans effectively tracks CCA progression in mice, providing valuable insights into cancer development and investigating potential treatments. Cholangiocarcinoma (CCA) is a type of primary liver cancer originating from the biliary tract epithelium, characterized by limited treatment options for advanced cases and low survival rates. This study aimed to establish an orthotopic mouse model for CCA and monitor tumor growth using PET/MR imaging. Murine CCA cells were implanted into the liver lobe of male C57BL/6J mice. The imaging groups included contrast-enhanced (CE) MR, CE-MR with static [18F]FDG-PET, and dynamic [18F]FDG-PET. Tumor volume and FDG uptake were measured weekly over four weeks. Early tumor formation was visible in CE-MR images, with a gradual increase in volume over time. Dynamic FDG-PET revealed an increase in the metabolic glucose rate (MRGlu) over time. Blood analysis showed pathological changes in liver-related parameters. Lung metastases were observed in nearly all animals after four weeks. The study concludes that PET-MR imaging effectively monitors tumor progression in the CCA mouse model, providing insights into CCA development and potential treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Gliomas are the most common type of malignant brain tumors in adults. They are frequently heterogeneous, containing regions of varying properties and aggressiveness. It can be challenging to define the tumor borders and identify the most aggressive parts of the tumor based on MRI alone. This study investigates whether PET imaging with amino acid tracer [18F]-FACBC can provide additional information on the composition of the tumor. The results suggest that uptake of the tracer could be used to identify aggressive tumor tissue with high accuracy, and with higher sensitivity than that of contrast-enhanced MRI. Background: Gliomas have a heterogeneous nature, and identifying the most aggressive parts of the tumor and defining tumor borders are important for histomolecular diagnosis, surgical resection, and radiation therapy planning. This study evaluated [18F]-FACBC PET for glioma tissue classification. Methods: Pre-surgical [18F]-FACBC PET/MR images were used during surgery and image-localized biopsy sampling in patients with high- and low-grade glioma. TBR was compared to histomolecular results to determine optimal threshold values, sensitivity, specificity, and AUC values for the classification of tumor tissue. Additionally, PET volumes were determined in patients with glioblastoma based on the optimal threshold. [18F]-FACBC PET volumes and diagnostic accuracy were compared to ce-T1 MRI. In total, 48 biopsies from 17 patients were analyzed. Results: [18F]-FACBC had low uptake in non-glioblastoma tumors, but overall higher sensitivity and specificity for the classification of tumor tissue (0.63 and 0.57) than ce-T1 MRI (0.24 and 0.43). Additionally, [18F]-FACBC TBR was an excellent classifier for IDH1-wildtype tumor tissue (AUC: 0.83, 95% CI: 0.71–0.96). In glioblastoma patients, PET tumor volumes were on average eight times larger than ce-T1 MRI volumes and included 87.5% of tumor-positive biopsies compared to 31.5% for ce-T1 MRI. Conclusion: The addition of [18F]-FACBC PET to conventional MRI could improve tumor classification and volume delineation. [ABSTRACT FROM AUTHOR]

Simple Summary: In contrast to external beam radiation therapy, our understanding of the dose–response relationship in radiopharmaceutical therapy (RPT) remains limited. Given that the estimation of radiation-induced deoxyribonucleic acid (DNA) damage can correlate with various biological responses, nanoscale dosimetry emerges as a critical tool in lighting this intricate relationship. In this study, we developed a novel simulation-based nanoscale dosimetry platform by identifying optimal DNA physics models and benchmarking against existing data. Leveraging this platform, we conducted a case study to estimate DNA damage, thereby enhancing our comprehension of RPT effects at nanoscales. This research serves as a foundation for future studies on how RPT affects DNA at the nano-level, potentially improving cancer treatment strategies. Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose–response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125. We compared the energy deposition and single strand break (SSB) yield at each base pair location in a short B-form DNA (B-DNA) geometry with existing simulation and experimental data, considering both physical direct and chemical indirect hits. Additionally, we evaluated dosimetric differences between our high-resolution B-DNA target and a previously published simple B-DNA geometry. Overall, our benchmarking results for SSB yield from I-125 decay exhibited good agreement with both simulation and experimental data. Using this simulation, we then evaluated the SSB and double strand break (DSB) yields caused by a theranostic Br-77-labeled poly ADP ribose polymerase (PARP) inhibitor radiopharmaceutical. The results indicated a predominant contribution of chemical indirect hits over physical direct hits in generating SSB and DSB. This study lays the foundation for future investigations into the nano-dosimetric properties of RPT. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent approval of [177Lu]Lu-prostate-specific membrane antigen (PSMA) for managing metastatic castration-resistant prostate cancer (mCRPC) has catalyzed the innovation of various PSMA-targeted radiopharmaceuticals. In our retrospective study, we explored both safety and efficacy of two beta-emitting PSMA radioligands, [177Lu]Lu and [161Tb]Tb, for mCRPC therapy. Our study included 53 patients and reinforced prior evidence validating the clinical safety and efficacy of these radioligands. Our research suggested that these treatments are characterized by a favorable safety profile with negligible toxicity. Moreover, [161Tb]Tb-PSMA recipients, though trialed in a smaller patient sample, yielded concordant outcomes on par with those receiving [177Lu]Lu-PSMA, highlighting its promise as an alternative therapy and warrants additional investigation. The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally. [ABSTRACT FROM AUTHOR]

Simple Summary: Richter transformation (RT) is characterized by the transformation of CCL in the aggressive lymphoma variant with a significant worsening in prognosis. Initial reports about a substantial impact of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in predicting RT are available in the literature. Using data from 15 published studies, including 1593 CLL patients, we demonstrated that 2-[18F]FDG uptake expressed as the maximum standardized uptake value (SUVmax) has a high negative predictive value. Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: This manuscript systematically reviews the role of positron emission tomography (PET) in the assessment of toxicity associated with chimeric antigen receptor T-cell therapy (CAR T-cell therapy). CAR T-cell therapy, a revolutionary form of immunotherapy, activates immune mechanisms against malignant cells. By doing so, it can also provoke immune-mediated responses against healthy tissues. These responses exhibit diverse clinical, radiological, and functional manifestations across multiple physiological systems. Adverse events include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Both can cause life-threatening complications. Given the critical imperative of timely identification and vigilant monitoring of these adverse events to enable targeted interventions, PET has emerged as an indispensable imaging biomarker facilitating their detection, prediction, and surveillance. Hence, our investigation is specifically tailored to examine the utility of PET in evaluating adverse events induced by CAR T-cell therapy. The utilization of chimeric antigen receptor (CAR) T-cell therapy to target cluster of differentiation (CD)19 in cancer immunotherapy has been a recent and significant advancement. Although this approach is highly specific and selective, it is not without complications. Therefore, a systematic review was conducted to assess the current state of positron emission tomography (PET) in evaluating the adverse effects induced by CAR T-cell therapy. A thorough search of relevant articles was performed in databases such as PubMed, Scopus, and Web of Science up until March 2024. Two reviewers independently selected articles and extracted data, which was then organized and categorized using Microsoft Excel. The risk of bias and methodological quality was assessed. In total, 18 articles were examined, involving a total of 753 patients, in this study. A wide range of utilities were analyzed, including predictive, correlative, and diagnostic utilities. While positive outcomes were observed in all the mentioned areas, quantitative analysis of the included studies was hindered by their heterogeneity and use of varying PET-derived parameters. This study offers a pioneering exploration of this promising field, with the goal of encouraging further and more focused research in upcoming clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is the leading cause of death due to gynecologic malignancies. Peritoneal metastases represent the most common pathway for the spread of OC, both at the time of initial diagnosis and at recurrence. Accurate mapping of peritoneal metastases helps in planning the appropriate therapeutic strategy, predicting the likelihood of optimal cytoreduction, and identifying potentially unresectable or difficult disease sites that may require surgical technique modifications. Preoperative diagnostic work-up with multidetector CT (MDCT), MRI, including diffusion-weighted imaging (DWI), or FDG PET/CT plays a vital role in the accurate assessment of the extent of peritoneal carcinomatosis. In this article, the aim was to update the role of MDCT, MRI, including DWI, and FDG PET/CT in the detection of peritoneal metastases in ovarian cancer by conducting a systematic review and meta-analysis of the existing literature. This review aims to compare the diagnostic performance of multidetector CT (MDCT), MRI, including diffusion-weighted imaging, and FDG PET/CT in the detection of peritoneal metastases (PMs) in ovarian cancer (OC). A comprehensive search was performed for articles published from 2000 to February 2023. The inclusion criteria were the following: diagnosis/suspicion of PMs in patients with ovarian/fallopian/primary peritoneal cancer; initial staging or suspicion of recurrence; MDCT, MRI and/or FDG PET/CT performed for the detection of PMs; population of at least 10 patients; surgical results, histopathologic analysis, and/or radiologic follow-up, used as reference standard; and per-patient and per-region data and data for calculating sensitivity and specificity reported. In total, 33 studies were assessed, including 487 women with OC and PMs. On a per-patient basis, MRI (p = 0.03) and FDG PET/CT (p < 0.01) had higher sensitivity compared to MDCT. MRI and PET/CT had comparable sensitivities (p = 0.84). On a per-lesion analysis, no differences in sensitivity estimates were noted between MDCT and MRI (p = 0.25), MDCT and FDG PET/CT (p = 0.68), and MRI and FDG PET/CT (p = 0.35). Based on our results, FDG PET/CT and MRI are the preferred imaging modalities for the detection of PMs in OC. However, the value of FDG PET/CT and MRI compared to MDCT needs to be determined. Future research to address the limitations of the existing studies and the need for standardization and to explore the cost-effectiveness of the three imaging modalities is required. [ABSTRACT FROM AUTHOR]

Simple Summary: This clinical study explored the use of the positron emission tomography radiotracer, [18F]FSPG, for cancer imaging. [18F]FSPG measures a process involved in antioxidant production, which is important for cancer prognosis. We compared the distribution of this imaging agent in subjects with head and neck squamous cell cancer (HNSCC) and non-small-cell lung cancer (NSCLC). Results showed similar distribution in healthy organs but varied uptake in tumors, both between subjects and across different lesions. Although [18F]FSPG PET/CT offers insights into individual tumor behavior, its diagnostic potential is limited due to this variability in tumor uptake. Variability in [18F]FSPG retention, however, may provide crucial information about how tumors respond to therapy and mechanisms of treatment resistance. Background: (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography/computed tomography (PET/CT) provides a readout of system xc− transport activity and has been used for cancer detection in clinical studies of different cancer types. As system xc− provides the rate-limiting precursor for glutathione biosynthesis, an abundant antioxidant, [18F]FSPG imaging may additionally provide important prognostic information. Here, we performed an analysis of [18F]FSPG radiotracer distribution between primary tumors, metastases, and normal organs from cancer patients. We further assessed the heterogeneity of [18F]FSPG retention between cancer types, and between and within individuals. Methods: This retrospective analysis of prospectively collected data compared [18F]FSPG PET/CT in subjects with head and neck squamous cell cancer (HNSCC, n = 5) and non-small-cell lung cancer (NSCLC, n = 10), scanned at different institutions. Using semi-automated regions of interest drawn around tumors and metastases, the maximum standardized uptake value (SUVmax), SUVmean, SUV standard deviation and SUVpeak were measured. [18F]FSPG time–activity curves (TACs) for normal organs, primary tumors and metastases were subsequently compared to 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT at 60 min post injection (p.i.). Results: The mean administered activity of [18F]FSPG was 309.3 ± 9.1 MBq in subjects with NSCLC and 285.1 ± 11.3 MBq in those with HNSCC. The biodistribution of [18F]FSPG in both cohorts showed similar TACs in healthy organs from cancer patients. There was no statistically significant overall difference in the average SUVmax of tumor lesions at 60 min p.i. for NSCLC (8.1 ± 7.1) compared to HNSCC (6.0 ± 4.1; p = 0.29) for [18F]FSPG. However, there was heterogeneous retention between and within cancer types; the SUVmax at 60 min p.i. ranged from 1.4 to 23.7 in NSCLC and 3.1–12.1 in HNSCC. Conclusion: [18F]FSPG PET/CT imaging from both NSCLC and HNSCC cohorts showed the same normal-tissue biodistribution, but marked tumor heterogeneity across subjects and between lesions. Despite rapid elimination through the urinary tract and low normal-background tissue retention, the diagnostic potential of [18F]FSPG was limited by variability in tumor retention. As [18F]FSPG retention is mediated by the tumor's antioxidant capacity and response to oxidative stress, this heterogeneity may provide important insights into an individual tumor's response or resistance to therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Until recently, radiopharmaceuticals have been underutilized for the curative or the palliative treatment of cancer. Advances in a development program with investigational agents that have a radioactive payload as part of the studied drug product necessitate new ways of drug handling and administration as well as novel logistics for a safe and satisfactory patient experience. This review offers a roadmap for the clinical start-up and implementation of an integrated and leveraged programmatic collaboration for an academic theranostic center. Within this roadmap, there are complex issues of logistics, coordination, medical considerations, radioprotection, receipt and waste of radioactive agents, and patient release priorities. Regulatory agency input also adds to the layout dynamics of the theranostic center, but this roadmap does not cover specific requirements as United States state laws differ considerably. Radiation oncologists, radiopharmacists, nuclear medicine physicians, and medical oncologists have seen a renewed clinical interest in radiopharmaceuticals for the curative or the palliative treatment of cancer. To allow for the discovery and the clinical advancement of targeted radiopharmaceuticals, these stakeholders have reformed their trial efforts and remodeled their facilities to accommodate the obligations of a program centered upon radioactive investigational drug products. Now considered informally as drugs and not beam radiotherapy, radiopharmaceuticals can be more easily studied in the traditional clinical trial enterprise ranging from phase 0–I to phase III studies. Resources and physical facilities allocated to radiopharmaceuticals have brought forth new logistics and patient experience for safe and satisfactory drug delivery. The clinical use of theranostic agents—that is, diagnostic and therapeutic radionuclide pairs—has accelerated radiopharmaceutical development. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidental pituitary hypermetabolism on 18F-FDG PET/CT should be further evaluated for discriminating between pathologic and physiologic uptake, but a recent study suggests that pituitary hypermetabolism is common in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid hormone withdrawal (THW). The aim of this retrospective study was to compare pituitary metabolism in patients with DTC undergoing 18F-FDG PET/CT under THW versus recombinant human thyroid-stimulating hormone (rhTSH) stimulation. We confirmed a higher pituitary SUVmax and SUVratio with a higher prevalence of pituitary hypermetabolism in the THW group compared to the rhTSH group. A positive correlation between serum TSH levels and pituitary SUVmax was observed only in the THW group. The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation that could trigger unnecessary investigations. Background: 18F-FDG PET/CT is performed for the assessment of radioactive iodine non-avid disease in patients with DTC. In patients prepared by THW, increased pituitary uptake of 18F-FDG in the absence of pituitary disease may reflect the physiological activation of pituitary thyrotroph cells by hypothyroidism. This study aimed to compare pituitary 18F-FDG uptake in patients with DTC under THW vs. rhTSH stimulation. Methods: A total of 57 patients with DTC undergoing 18F-FDG PET/CT (40 under THW and 17 under rhTSH stimulation) were retrospectively analyzed. Pituitary metabolism was expressed as maximum standardized uptake value (SUVmax) and as SUVratio using the right cerebellum as reference. Results: Pituitary hypermetabolism (SUVmax ≥ 4.1) was present in more patients in the THW group compared to the rhTSH group (62.5% vs. 23.5%; p = 0.01). Pituitary metabolism was significantly higher in the THW group compared to the rhTSH group, as assessed by either SUVmax (mean ± SD: 4.61 ± 1.22, 95%CI: 4.22–5.00 vs. 3.34 ± 0.86, 95%CI: 2.9–3.8; p < 0.001) or SUVratio (0.52 ± 0.11, 95%CI: 0.49–0.56 vs. 0.42 ± 0.07, 95%CI: 0.38–0.46; p < 0.001). Serum TSH levels correlated positively with SUVmax (r = 0.41, p < 0.01) and SUVratio (r = 0.44, p < 0.01) in the THW group only. Conclusions: The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates a promising avenue for improving the diagnosis and treatment of triple-negative breast cancer (TNBC), a highly aggressive form of breast cancer with limited therapeutic options. The researchers focus on the prostate-specific membrane antigen (PSMA), known for its presence in prostate cancer but also identified in breast cancer. Using 18F-PSMA-1007 PET/CT, the study aims to assess PSMA's in vivo expression in TNBC patients and compare it with the standard [18F]FDG PET/CT. The findings suggest that [18F]PSMA-1007 PET/CT may outperform current methods in detecting distant metastases, especially in the brain. This research not only enhances our understanding of PSMA expression in TNBC but also hints at potential advancements in diagnostic imaging and targeted therapies for this challenging cancer type. Background: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. Methods: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. Results: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. Conclusions: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors, presenting in often challenging clinical scenarios, and require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for imaging well-differentiated neuroendocrine tumors NETs, and labelled with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and criteria for peptide receptor radionuclide therapy (PRRT) eligibility of based on somatostatin receptor (SSTR) expression. The present paper is an overview of currently employed radiolabeled SSTR analogues used for both diagnosis and therapy of NENs. Further emerging radiopharmaceuticals targeting SSTRs (e.g., fluorinated SSTR agonists, radiolabeled SSTR antagonists) as well as strategies to improve PRRT efficacy (by means of implementation of personalized treatment schemes, dosimetry, amelioration of response assessment strategies, and optimization of treatment sequencing) are also discussed. Finally, although very preliminary, some studies employing radiomic features in various kinds of NET are reported. Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs. [ABSTRACT FROM AUTHOR]

Simple Summary: Synchronous oligometastatic non-small cell lung cancer (NSCLC) represents an intermediate state of metastatic disease with a limited number of metastases. It has been suggested that adding local radical treatment (LRT) in this setting may improve the survival outcomes, but there are no validated tools to better select those patients who are most likely to benefit from LRT. The presence of cachexia and sarcopenia at diagnosis seems to be linked to poorer outcomes in local or advanced NSCLC, but it is not clear if these factors can be used to guide the treatment decisions in oligometastatic NSCLC and to preclude a possible radical treatment in patients with baseline cachexia or sarcopenia. For this reason, we evaluated the impact of cachexia and sarcopenia on survival outcomes and toxicities in a group of patients with synchronous oligometastatic NSCLC on an intention-to-treat basis. Considering the different definitions of sarcopenia used among different studies, we used the Psoas Muscle Index (PMI) as a surrogate of sarcopenia. Progression-free survival was longer for patients without cachexia and sarcopenia compared to those with cachexia and/or sarcopenia. Among patients with advanced NSCLC, there is a group of patients with synchronous oligometastatic disease (sOMD), defined as a limited number of metastases detected at the time of diagnosis. As cachexia and sarcopenia are linked to poor survival, incorporating this information could assist clinicians in determining whether a radical treatment should be administered. In a retrospective multicenter study, including all patients with adequately staged (FDG-PET, brain imaging) sOMD according to the EORTC definition, we aimed to assess the relationship between cachexia and/or sarcopenia and survival. Of the 439 patients that were identified between 2015 and 2021, 234 met the criteria for inclusion and were included. The median age of the cohort was 67, 52.6% were male, and the median number of metastasis was 1. Forty-six (19.7%) patients had cachexia, thirty-four (14.5%) had sarcopenia and twenty-one (9.0%) had both. With a median follow-up of 49.7 months, median PFS and OS were 8.6 and 17.3 months, respectively. Moreover, a trend toward longer PFS was found in patients without cachexia and sarcopenia compared to those with cachexia and/or sarcopenia. In multivariate analysis, cachexia and sarcopenia were not associated with an inferior survival, irrespective of receiving radical treatment. High CRP was associated with inferior survival and could be a prognostic factor, helping the decision of clinicians in selecting patients who may benefit from the addition of LRT. However, despite the homogeneous definition of oligometastatic disease and the adequate staging, our subgroups were small. Therefore, further studies are needed to better understand our hypothesis and generating findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant melanoma is a highly aggressive malignancy, accounting for the majority of skin cancer deaths. Its global incidence rate has been increasing rapidly over the past few decades, and accurate disease diagnosis is crucial for optimal patient management. Imaging modalities, such as positron emission tomography (PET), play a pivotal role in accomplishing this objective. Based on current guidelines, [18F]F-FDG PET is recommended for the assessment of distant metastases in advanced-stage melanoma patients. In addition, it is indicated in patient follow-up. However, to our knowledge, there is no comprehensive investigation in the literature reporting the real-world performance of [18F]F-FDG PET in melanoma patients across a broad spectrum of clinical scenarios. Thus, we aimed to describe the performance of [18F]F-FDG PET in a wide range of detection-based clinical scenarios (e.g., initial staging, re-staging, locoregional detection, distant metastasis diagnosis) by conducting a systematic review and meta-analysis of the existing literature. We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18F]F-FDG-PET and compared it with a valid reference standard were considered eligible. The pooled measurements were calculated based on the data level (patient/lesion-based). Regarding sub-groups, diagnostic performances were calculated for local, regional and distant involvement. The bivariate model was employed to calculate sensitivity and specificity. The initial search resulted in 6678 studies. Finally, 100 entered the meta-analysis, containing 82 patient-based (10,403 patients) and 32 lesion-based (6188 lesions) datasets. At patient level, overall, [18F]F-FDG-PET had pooled sensitivity and specificity of 81% (95%CI: 73–87%) and 92% (95%CI: 90–94%), respectively. To detect regional lymph node metastasis, the pooled sensitivity and specificity were 56% (95%CI: 40–72%) and 97% (95%CI: 94–99%), respectively. To detect distant metastasis, they were 88% (95%CI: 81–93%) and 94% (95%CI: 91–96%), respectively. At lesion level, [18F]F-FDG-PET had a pooled sensitivity and specificity of 70% (95%CI: 57–80%) and 94% (95%CI: 88–97%), respectively. Thus, [18F]F-FDG-PET is a valuable diagnostic modality for melanoma assessment. It was accurate in various clinical scenarios. However, despite its high specificity, it showed low sensitivity in detecting regional lymph node metastasis and could not replace lymph node biopsy. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation is emerging as a treatment option for patients with colorectal liver metastases. Due to the lack of liver donors, patient selection is vital. In this study, we report on the predictive value of combining metabolic tumor volume obtained from the pre-transplantation 18F-FDG PET/CT with the radiological measurements of tumor load (size, number, and tumor burden score) to select patients with the probability of long-term survival. Patients with low metabolic tumor volume have long disease-free survival, overall survival, and survival after relapse despite a high number of liver metastases and a high tumor burden score. This underlines the prognostic properties of metabolic active-tumor burden beyond conventional measurements. The aim of the present study is to report on the ability of metabolic tumor volume (MTV) of liver metastases from pre-transplant 18F-FDG PET/CT in combination with conventional radiological measurements from CT scans to predict long-term disease-free survival (DFS), overall survival (OS), and survival after relapse (SAR) after liver transplantation for colorectal liver metastases. The total liver MTV was obtained from the 18F-FDG PET/CT, and the size of the largest metastasis and the total number of metastases were obtained from the CT. DFS, OS, and SAR for patients with a low and high MTV, in combination with a low and high size, number, and tumor burden score, were compared using the Kaplan–Meier method and log–rank test. Patients with a low number of metastases and low MTV had a significantly longer OS than those with a high MTV, with a median survival of 151 vs. 26 months (p = 0.010). Patients with a high number of metastases and low MTV had significantly longer DFS, OS, and SAR than patients with a high MTV (p = 0.034, 0.006, and 0.026). The tumor burden score of group/zone 3, in combination with a low MTV, had a significantly improved DFS, OS, and SAR compared to those with a high MTV (p = 0.034, <0.001, and 0.006). Patients with a low MTV of liver metastases had a long DFS, OS, and SAR despite a high number of liver metastases and a high tumor burden score. [ABSTRACT FROM AUTHOR]

Simple Summary: Fluorine-18-fluorodeoxyglucose positron emission computed tomography/computed tomography (18F-FDG PET/CT) imaging is crucial for staging, restaging, and therapeutic response assessment in colorectal cancer (CRC) patients. However, 18F-FDG is not specific for malignant lesions. Dual-time-point imaging has emerged as a promising tool to address this limitation. Our findings indicate that delayed PET/CT images significantly increased both sensitivity (87.7% vs. 100%) and specificity (94% vs. 91%) compared to standard early images. Therefore, our study demonstrated the added value of dual-time-point scans with little extra cost and radiation exposure. Objective: The aim of this study was to evaluate the diagnostic performance of dual-time-point fluorine-18-fluorodeoxyglucose positron emission computed tomography/computed tomography (18F-FDG PET/CT) compared to conventional early imaging for detecting colorectal liver metastases (CRLM) in colorectal cancer (CRC) patients. Methods: One hundred twenty-four consecutive CRC patients underwent dual-time-point imaging scans on a retrospective basis. Histopathological confirmation and/or clinical follow-up were accepted as the gold standard. Standard uptake values (SUV), signal-to-noise ratio (SNR), retention index (RI), tumor-to-normal liver ratio (TNR), and lesion sizes were measured for early and delayed PET scans. The diagnostic performance of early and delayed images was calculated on a per-patient basis and compared using McNemar's test. Results: Among the 124 patients, 57 (46%) had CRLM, 6 (4.8%) had benign lesions, and 61 (49.2%) had no concerning lesions detected. Smaller CRLM lesions (<5 cm3) showed significantly higher uptake in the delayed scans relative to early imaging (p < 0.001). The SUV and TNR increased significantly in delayed imaging of all metastatic lesions (p < 0.001). The retention index of all CRLM was high (40.8%), especially for small lesions (54.8%). A total of 177 lesions in delayed images and 124 in standard early images were identified. In a per-patient analysis, delayed imaging had significantly higher sensitivity (100% vs. 87.7%) and specificity (91.0% vs. 94.0%) compared to early imaging (p-value = 0.04). Conclusions: The detection of liver lesions using dual-time-point PET/CT scan improves the sensitivity and specificity for the detection of colorectal liver metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis for metastatic prostate cancer patients remains poor. Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and is a promising target for both imaging and therapy. In this review paper, we provide an overview of the evidence for PSMA-targeted imaging in prostate cancer, focusing on different imaging modalities and their theranostic applications. We will also review PSMA-targeted radioligand therapy, focusing on lutetium-177 radioligand therapy and alpha-emitting radioligand therapy with actinium-225. Combination regimens with lutetium-177 and other systemic therapy agents will be reviewed. Antibody-based radioimmunotherapy will also be discussed along with other noteworthy radionuclide agents. Introduction: Prostate-specific membrane antigen (PSMA) is a promising novel molecular target for imaging diagnostics and therapeutics (theranostics). There has been a growing body of evidence supporting PSMA theranostics approaches in optimizing the management of prostate cancer and potentially altering its natural history. Methods: We utilized PubMed and Google Scholar for published studies, and clinicaltrials.gov for planned, ongoing, and completed clinical trials in PSMA theranostics as of June 2021. We presented evolving evidence for various PSMA-targeted radiopharmaceutical agents in the treatment paradigm for prostate cancer, as well as combination treatment strategies with other targeted therapy and immunotherapy. We highlighted the emerging evidence of PSMA and fluorodeoxyglucose (FDG) PET/CT as a predictive biomarker for PSMA radioligand therapy. We identified seven ongoing clinical trials in oligometastatic-directed therapy using PSMA PET imaging. We also presented a schematic overview of 17 key PSMA theranostic clinical trials throughout the various stages of prostate cancer. Conclusions: In this review, we presented the contemporary and future landscape of theranostic applications in prostate cancer with a focus on PSMA ligands. As PSMA theranostics will soon become the standard of care for the management of prostate cancer, we underscore the importance of integrating nuclear medicine physicians into the multidisciplinary team. [ABSTRACT FROM AUTHOR]

Simple Summary: Boron neutron capture therapy (BNCT) is an emerging anticancer treatment. The success of BNCT relies on the delivery of adequate quantities of 10B to tumor cells. Carboranes, polyhedral clusters containing boron, carbon and hydrogen atoms, are promising candidates as boron agents in BNCT. In this review, we provide an overview and state-of-the-art description of applications of carboranes for in vivo BNCT studies. We comprehensively report: (i) the different molecules used, (ii) their formulation and administration strategies, (iii) the tumor models investigated and (iv) qualitative and quantitative methodologies for carborane detection in in vivo experiments. Carboranes have emerged as one of the most promising boron agents in boron neutron capture therapy (BNCT). In this context, in vivo studies are particularly relevant, since they provide qualitative and quantitative information about the biodistribution of these molecules, which is of the utmost importance to determine the efficacy of BNCT, defining their localization and (bio)accumulation, as well as their pharmacokinetics and pharmacodynamics. First, we gathered a detailed list of the carboranes used for in vivo studies, considering the synthesis of carborane derivatives or the use of delivery system such as liposomes, micelles and nanoparticles. Then, the formulation employed and the cancer model used in each of these studies were identified. Finally, we examined the analytical aspects concerning carborane detection, identifying the main methodologies applied in the literature for ex vivo and in vivo analysis. The present work aims to identify the current strengths and weakness of the use of carboranes in BNCT, establishing the bottlenecks and the best strategies for future applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine prostate cancer is a rare neoplasm with aggressive behavior and poor prognosis. Its diagnostic approach is challenging since no specific features are present when using conventional imaging or positron emission tomography (PET). The aim of this systematic review was, therefore, to evaluate the role of these imaging modalities for the assessment of neuroendocrine prostate cancer. At present, it is still uncertain which tracer performs best, and although [18F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting. Background: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. Results: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [18F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [68Ga]Ga-FAPI-04, [68Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. Conclusion: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [18F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Radioiodine therapy is the main treatment option for metastatic differentiated thyroid cancer (DTC). However, only half of these patients achieve (partial or complete) remission or have stable disease during long-term follow-up. In the remaining ones, disease progresses mainly as they become radioiodine-refractory. The diagnostics of radioiodine-refractory disease are extensively debated. The introduction of novel tracers besides radioiodine isotopes (131I, 123I, and 124I) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) opens new options for the diagnostics and therapy of this subgroup of DTC patients. Prostate-specific membrane antigen (PSMA) ligands, fibroblast activation protein inhibitors (FAPI), and somatostatin receptor-targeted radiopharmaceuticals appear to be new potential theranostics tracers. In this review, we will elaborate on the role of these radiopharmaceuticals in the management of radioiodine-refractory disease. Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [18F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC. [ABSTRACT FROM AUTHOR]

Simple Summary: [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) provides information about metabolic patterns of different diseases and conditions. This study aimed to prospectively evaluate patients with breast cancer in order to describe specific brain metabolic patterns related to the presence or absence of primary forms of headache, namely tension-type headache (TTH) and migraine (MiG). Moreover, we explored the association between primary headache forms and BC response to neoadjuvant chemotherapy (NAC). We observed a high rate of headache in the 46 BC analyzed patients. TTH patients exhibited areas of hypometabolism in specific brain regions before NAC. Moreover, our results suggest an association between primary headache, especially MiG, and treatment response to NAC. Collectively, our results support the hypothesis of a complex and dynamic interplay among BC, headache, and hormonal status. This study aimed to examine brain metabolic patterns on [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) in breast cancer (BC), comparing patients with tension-type headache (TTH), migraine (MiG), and those without headache. Further association with BC response to neoadjuvant chemotherapy (NAC) was explored. In this prospective study, BC patients eligible for NAC performed total-body [18F]FDG PET/CT with a dedicated brain scan. A voxel-wise analysis (two-sample t-test) and a multiple regression model were used to compare brain metabolic patterns among TTH, MiG, and no-headache patients and to correlate them with clinical covariates. A single-subject analysis compared each patient's brain uptake before and after NAC with a healthy control group. Primary headache was diagnosed in 39/46 of BC patients (39% TTH and 46% MiG). TTH patients exhibited hypometabolism in specific brain regions before NAC. TTH patients with a pathological complete response (pCR) to NAC showed hypermetabolic brain regions in the anterior medial frontal cortex. The correlation between tumor uptake and brain metabolism varied before and after NAC, suggesting an inverse relationship. Additionally, the single-subject analysis revealed that hypometabolic brain regions were not present after NAC. Primary headache, especially MiG, was associated with a better response to NAC. These findings suggest complex interactions between BC, headache, and hormonal status, warranting further investigation in larger prospective cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: The assessment of responses is critical in patients diagnosed with multiple myeloma. Nowadays, one of the most informative parameters to discriminate responses to treatment and prognosis is minimal residual disease (MRD). Several strategies may be used to detect and quantify MRD; some of them have been widely used and standardized, but we can find additional strategies lacking such an extensive validation process. Here, we present a summary of the current state of the art of MRD detection in multiple myeloma and future directions in the field. Responses to treatment have improved over the last decades for patients with multiple myeloma. This is a consequence of the introduction of new drugs that have been successfully combined in different clinical contexts: newly diagnosed, transplant-eligible or ineligible patients, as well as in the relapsed/refractory setting. However, a great proportion of patients continue to relapse, even those achieving complete response, which underlines the need for updated response criteria. In 2014, the international myeloma working group established new levels of response, prompting the evaluation of minimal residual disease (MRD) for those patients already in complete or stringent complete response as defined by conventional serological assessments: the absence of tumor plasma cells in 100,000 total cells or more define molecular and immunophenotypic responses by next-generation sequencing and flow cytometry, respectively. In this review, we describe all the potential methods that may be used for MRD detection based on the evidence found in the literature, paying special attention to their advantages and pitfalls from a critical perspective. [ABSTRACT FROM AUTHOR]

Simple Summary: Background: Previous studies reported mitochondrial and endoplasmic reticulum (ER) redox stress in Circulating mononucleated cells (PBMCs) of patients with Hodgkin lymphoma (HL) display an oxidative damage to the endoplasmic reticulum. Here, we assessed whether the redox stress also characterizes tissues not directly involved in the inflammatory response and extends to non-HL (NHL) patients. Mitochondrial reactive oxygen species generation and malondialdehyde levels were increased only in the PBMCs of HL patients. These same cells also showed an enhanced activity of the hexose-6P-dehydrogenase (H6PD) and thus of a pentose phosphate pathway selectively confined within the ER. H6PD regulates the uptake of the most widely used tracer in clinical oncology: 18F-fluoro-deoxyglucose whose uptake was remarkably increased in the heart of HL patients. These data thus document that HL is associated with a high redox stress involving the ER. This feature does not apply to NHL. It is not limited to the PBMCs, and rather involves the myocardium as an epitome of tissues not participating to the inflammatory response to the disease. Background: Previous studies reported mitochondrial and endoplasmic reticulum redox stress in peripheral blood mononucleated cells (PBMCs) of treatment-naïve Hodgkin lymphoma (HL) patients. Here, we assessed whether this response also applies to non-HL (NHL) patients, and whether the oxidative damage is a selective feature of PBMCs or, rather, also affects tissues not directly involved in the inflammatory response. Methods: Isolated PBMCs of 28 HL, 9 diffuse large B cell lymphoma, 8 less aggressive-NHL, and 45 controls underwent flow cytometry to evaluate redox stress and uptake of the glucose analogue 2-NBDG. This analysis was complemented with the assay of malondialdehyde (MDA) levels and enzymatic activity of glucose-6P-dehydrogenase and hexose-6P-dehydrogenase (H6PD). In all lymphoma patients, 18F-fluoro-deoxyglucose uptake was estimated in the myocardium and skeletal muscles. Results: Mitochondrial reactive oxygen species generation and MDA levels were increased only in HL patients as well as H6PD activity and 2-NBDG uptake. Similarly, myocardial FDG retention was higher in HL than in other groups as opposed to a similar tracer uptake in the skeletal muscle. Conclusions: Redox stress of PBMCs is more pronounced in HL with respect to both NHL groups. This phenomenon is coherent with an increased activity of H6PD that also extends to the myocardium. [ABSTRACT FROM AUTHOR]

Simple Summary: Adrenal masses represent a common incidental finding at imaging exams such as computed tomography (CT) and magnetic resonance imaging performed for unrelated reasons. Encompassing both benign and malignant entities, these lesions can prove challenging to classify. 2-[18F]FDG PET-CT is a recognized imaging modality for the characterization of indeterminate adrenal masses, but it is an expensive imaging modality and involves radiation exposure. To reduce the number of required scans and identify a less invasive potential alternative, we investigated whether CT radiomics could be used to predict the diagnostic parameter obtained using 2-[18F]FDG PET-CT (namely SUVmax). However, in our retrospective cohort of 179 adrenal masses and 150 PET-CT scans (of which 66 without iodine contrast injection), no correlation was found between the radiomics synthetic value (RadSV) and 2-[18F]FDG PET-CT SUVmax. This preliminary finding suggests that it might not be possible to use CT radiomics to reduce 2-[18F]FDG PET-CT referrals, confirming the role as problem solving tool of this imaging modality. Background: Indeterminate adrenal masses (AM) pose a diagnostic challenge, and 2-[18F]FDG PET-CT serves as a problem-solving tool. Aim of this study was to investigate whether CT radiomics features could be used to predict the 2-[18F]FDG SUVmax of AM. Methods: Patients with AM on 2-[18F]FDG PET-CT scan were grouped based on iodine contrast injection as CT contrast-enhanced (CE) or CT unenhanced (NCE). Two-dimensional segmentations of AM were manually obtained by multiple operators on CT images. Image resampling and discretization (bin number = 16) were performed. 919 features were calculated using PyRadiomics. After scaling, unstable, redundant, and low variance features were discarded. Using linear regression and the Uniform Manifold Approximation and Projection technique, a CT radiomics synthetic value (RadSV) was obtained. The correlation between CT RadSV and 2-[18F]FDG SUVmax was assessed with Pearson test. Results: A total of 725 patients underwent PET-CT from April 2020 to April 2021. In 150 (21%) patients, a total of 179 AM (29 bilateral) were detected. Group CE consisted of 84 patients with 108 AM (size = 18.1 ± 4.9 mm) and Group NCE of 66 patients with 71 AM (size = 18.5 ± 3.8 mm). In both groups, 39 features were selected. No statisticallyf significant correlation between CT RadSV and 2-[18F]FDG SUVmax was found (Group CE, r = 0.18 and p = 0.058; Group NCE, r = 0.13 and p = 0.27). Conclusions: It might not be feasible to predict 2-[18F]FDG SUVmax of AM using CT RadSV. Its role as a problem-solving tool for indeterminate AM remains fundamental. [ABSTRACT FROM AUTHOR]

Simple Summary: We tried to use a small amount of radioactivity, injected around non-small cell lung cancers, to see if this technique can identify the lymph node receiving the flow (and thus potentially the metastases) from the tumour. Our results show that it is possible to do so; this technique could be used to obtain a personalised and potentially safer approach in lung cancer surgery. Background: Intraoperative localisation of nodal disease in non-small cell lung cancer (NSCLC) can be challenging. Lymph node localisation via radiopharmaceuticals is used in many conditions; we tested the feasibility of this approach in NSCLC. Methods: NSCLC patients were prospectively recruited. Intraoperative peri-tumoral injections of [99mTc]Tc-albumin nanocolloids were performed, followed by removing the tumour and locoregional lymph nodes. These were examined ex vivo with a gamma probe and labelled sentinel lymph nodes (SLNs) if they showed any activity or non-sentinel lymph nodes (nSLNs) if they did not. Thereafter, the surgical field was scanned with the probe; any further radioactive lymph node was removed and labelled as "extra" SLNs (eSLNs). All specimens were sent to histology, and metastatic status was recorded. Results: 48 patients were enrolled, and 290 nodal stations were identified: 179 SLNs, 87 nSLNs, and 24 eSLNs. A total of 44 nodal metastases were identified in 22 patients, with 36 of them (82%) located within SLNs. Patients with nSLNs metastases had at least a co-existing positive SLN. No metastases were found in eSLNs. Conclusions: The technique shows high sensitivity for intraoperative nodal metastases identification. This information could allow selective lymphadenectomies in low-risk patients or more aggressive approaches in high-risk patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This article discusses the use of peptide receptor radionuclide therapy (PRRT) as a key treatment method for advanced, unresectable neuroendocrine tumors. It covers the multidisciplinary theranostic approach, treatment effectiveness, patient outcomes, and toxicity of PRRT for neuroendocrine neoplasms. We will also examine important research, and explore new radiopharmaceuticals for the treatment of these patients. Neuroendocrine neoplasms (NENs) are tumors originating from neuroendocrine cells distributed throughout the human body. With an increasing incidence over the past few decades, they represent a highly heterogeneous group of neoplasms, mostly expressing somatostatin receptors (SSTRs) on their cell surface. Peptide receptor radionuclide therapy (PRRT) has emerged as a crucial strategy for treating advanced, unresectable neuroendocrine tumors by administering radiolabeled somatostatin analogs intravenously to target SSTRs. This article will focus on the multidisciplinary theranostic approach, treatment effectiveness (such as response rates and symptom relief), patient outcomes, and toxicity profile of PRRT for NEN patients. We will review the most significant studies, such as the phase III NETTER-1 trial, and discuss promising new radiopharmaceuticals, including alpha-emitting radionuclide-labeled somatostatin analogs and SSTR antagonists. [ABSTRACT FROM AUTHOR]

Simple Summary: In breast cancer (BC) patients, neoadjuvant chemotherapy (NAC) is chemotherapy given before surgery. Complete pathological response (pCR) to NAC is defined as the absence of residual tumor cells on microscopy both in the breast and in the axillary or distant lymph nodes in the surgical specimen. Achievement of pCR is associated with longer disease-free survival (DFS), namely survival without tumor recurrence. [18F]Fluorodeoxyglucose (18F-FDG) positron emission tomography may represent a complementary imaging tool in predicting pCR to NAC. We found (PET)-derived parameters predicting DFS in patients with BC with different molecular subtypes (based on the presence of specific receptors in the tumor). Furthermore, we demonstrated that some of these parameters predicting DFS are significantly different in patients achieving pCR compared to those without pCR after NAC. Larger study samples are needed to confirm these preliminary findings. We investigated whether baseline [18F] Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each 18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline 18F-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC. [ABSTRACT FROM AUTHOR]

Simple Summary: A lack of external validation is still one of the major limitations of radiomics, hampering its clinical translation. The aim of this study was to build and externally validate an [18F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma treated with preoperative afatinib. Radiomic analysis of two cohorts of 20 and 34 patients was performed, where each cohort served once as a training and once as an external validation set. The radiomic model was compared to a clinical model and to a model that combined clinical and radiomic features. The radiomic model surpassed the clinical model in terms of predictive performance, but the combination of the radiomic and clinical model performed best. The [18F]FDG-PET radiomic signature based on the evaluation scan seems promising for the prediction of overall survival in HNSSC treated with preoperative afatinib. Aim: To build and externally validate an [18F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Two multicentre datasets of patients with operable HNSCC treated with preoperative afatinib who underwent a baseline and evaluation [18F]FDG PET/CT scan were included (EORTC: n = 20, Unicancer: n = 34). Tumours were delineated, and radiomic features were extracted. Each cohort served once as a training and once as an external validation set for the prediction of overall survival. Supervised feature selection was performed using variable hunting with variable importance, selecting the top two features. A Cox proportional hazards regression model using selected radiomic features and clinical characteristics was fitted on the training dataset and validated in the external validation set. Model performances are expressed by the concordance index (C-index). Results: In both models, the radiomic model surpassed the clinical model with validation C-indices of 0.69 and 0.79 vs. 0.60 and 0.67, respectively. The model that combined the radiomic features and clinical variables performed best, with validation C-indices of 0.71 and 0.82. Conclusion: Although assessed in two small but independent cohorts, an [18F]FDG-PET radiomic signature based on the evaluation scan seems promising for the prediction of overall survival for HNSSC treated with preoperative afatinib. The robustness and clinical applicability of this radiomic signature should be assessed in a larger cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognostic stratification of patients affected by lymphomas is critical, and many positron-emission tomography (PET) metabolic parameters such as SUV, MTV, and TLG have been studied for this purpose. However, the lack of technical standardization in their measurements strongly affects their clinical power and potential integration into clinical practice. Dmax is a new biomarker that measures the distance between the two farthest hypermetabolic PET lesions and seems to show high accuracy as a prognostic factor in patients with lymphomas. The aim of this systematic review was to provide an evidence-based overview of the role of Dmax in lymphomas. Recently, several studies introduced the potential prognostic usefulness of maximum tumor dissemination (Dmax) measured by 2-deoxy-2-fluorine-18-fluoro-D-glucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Dmax is a simple three-dimensional feature that represents the maximal distance between the two farthest hypermetabolic PET lesions. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane libraries was conducted, including articles indexed up to 28 February 2023. Ultimately, 19 studies analyzing the value of 18F-FDG PET/CT Dmax in patients with lymphomas were included. Despite their heterogeneity, most studies showed a significant prognostic role of Dmax in predicting progression-free survival (PFS) and overall survival (OS). Some articles showed that the combination of Dmax with other metabolic features, such as MTV and interim PET response, proved to better stratify the risk of relapse or death. However, some methodological open questions need to be clarified before introducing Dmax into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) causes significant mortality globally. The majority of patients experience resistance to systemic therapies and often undergo recurrence or disease progression even after aggressive local therapies. Management of HCC is determined by the extent and stage of the disease using blood tests and imaging tests per the BCLC guidelines. A number of positron emission tomography (PET) radiopharmaceuticals have been investigated with the aim of finding the most appropriate biomarker, which can help to accurately stage the disease to optimise treatment of this cancer. More trials are necessary to determine the accuracy of these PET radiotracers and their impacts on initial staging, assessing the treatment response and determining recurrence early enough to minimise morbidity. Numerous positron emission tomography (PET) targets for detection and staging of hepatocellular cancer have been developed in recent years. Hepatocellular carcinomas (HCCs) are clinically and pathologically heterogeneous tumours with a high tendency to be aggressive and unresponsive to chemotherapy. Early detection is essential, and the need for an adequate imaging biomarker, which can overcome some of the limitations of conventional radiological imaging, is persistent. Flourine-18 (18F) flourodeoxyglucose (FDG), the most widely used PET radiopharmaceutical, has proven disappointing as a possible staple in the evaluation of HCC. This disappointment had led to experimentation with carious radiotracers, such as the choline derivatives, acetate, and prostate-specific membrane antigen, which appear to complement and/or enhance the role of FDG. In this study, we look at the various PET radiopharmaceuticals that have been used for imaging HCC and the particular pathways that they target in HCC and liver cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. Seventeen Italian centers analyzed the role of serial [18F]FDG PET/CT scans in patients candidates and, later undergoing immunotherapy for some solid cancers. Serial [18F]FDG PET/CT can be useful in evaluating the response to therapy, soon after 3 and 6-months from the start of immunotherapy. The evidences were foud both in patients affected by lung cancer and malignant melanoma, although large prospective trials are needed for definitively confirmed these findings. AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31–89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1–137) months, 113 (36.3%) patients had died. On Kaplan–Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory. [ABSTRACT FROM AUTHOR]

Simple Summary: Incomplete imaging response following non-surgical treatment for head and neck cancer is common, and optimal management is uncertain. This single-centre study assessed the value of performing a second PET-CT scan a few months later in patients with uncertain findings initially after treatment and showed that in most cases, the changes resolved or stayed the same and were not due to residual cancer. This approach could be used to spare unnecessary surgery when there is initial uncertainty. Background: Incomplete response on FDG PET-CT following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC) hinders optimal management. The study assessed the utility of an interval (second look) PET-CT. Methods: Patients with oropharyngeal squamous cell carcinoma cancer (OPSCC) treated with CRT at a single centre between 2013 and 2020 who underwent baseline, response, and second-look PET-CT were included. Endpoints were conversion rate to complete metabolic response (CMR) and test characteristics of second-look PET-CT. Results: In total, 714 patients with OPSCC underwent PET-CT post-radiotherapy. In total, 88 patients with incomplete response underwent second-look PET-CT a median of 13 weeks (interquartile range 10–15 weeks) after the initial response assessment. In total, 27/88 (31%) second-look PET-CTs showed conversion to CMR, primary tumour CMR in 20/60 (30%), and nodal CMR in 13/37 (35%). In total, 1/34 (3%) with stable tumour/nodal uptake at the second-look PET-CT relapsed. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of second-look PET-CT were 95%, 49%, 50%, and 95% for tumour and 92%, 50%, 50%, and 92% for nodes, respectively. Primary tumour progression following CMR occurred in one patient, two patients with residual nodal uptake at second-look PET-CT progressed locoregionally, and one patient developed metastatic disease following CMR in residual nodes. Conclusion: Most patients undergoing second-look PET-CT converted to CMR or demonstrated stable PET signal. NPV was high, suggesting the potential to avoid unnecessary surgical intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies in 24 cancer patients. Here, we apply a subgroup analysis to that dataset. Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). We conclude that multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Purpose: FAPI-PET is a promising imaging technique for various malignant as well as non-malignant pathologies. In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies. Here, we apply a subgroup analysis to that dataset and describe the tracer-wise uptake kinetic behavior of multiple types of FAPI-positive lesions, which are encountered frequently during clinical routine. Methods: A total of 24 cancer patients underwent whole-body FAPI-PET scans, and images were acquired at 10, 22, 34, 46 and 58 min after the administration of 150–250 MBq of 68Ga-FAPI tracer molecules (eight patients each regarding FAPI-02, FAPI-46 and FAPI-74). Standardized uptake values (SUVmax and SUVmean) of healthy tissues, cancer manifestations and non-malignant lesions were measured and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition timepoints. Results: Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). Furthermore, marked differences were found between the three tracer variants regarding their time-dependent uptake and TBRs within different subclasses of malignant, inflammatory/reactive and degenerative pathologies. Conclusion: Multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Differences in the kinetic behavior of malignant and benign pathologies can facilitate the interpretation of FAPI-positive lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: The effective role of sarcopenia and body changes during treatment in elderly (>65 years) Hodgkin lymphoma (HL) is unclear. The aim of our study was to analyze the longitudinal body changes in terms of muscle and adipose area measurement using the computed tomography (CT) of positron emission tomography (PET)/CT during and at the end of chemotherapy. Moreover, we examined the prognostic role of these parameters together with the main clinical and metabolic variables. The incidence of sarcopenia increased in elderly HL during the chemotherapy course, with, e.g., the gain of adipose tissue areas. [18F]FDG PET/CT features (metabolic response at interim and end-of-treatment), baseline sarcopenia, and body composition changes during chemotherapy may have a prognostic role, especially for overall survival. The aim of this retrospective study was to investigate the longitudinal body changes in terms of muscle and adipose areas and their prognostic role in elderly (>65 years) patients affected by Hodgkin lymphoma (HL). Skeletal muscle area (SMA), skeletal muscle index (SMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular adipose tissue (IMAT), and total dispose tissue (TAT) were measured using the computed tomography (CT) of fluorine-18-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT) in 88 patients who undertook baseline, interim (after two cycles of chemotherapy), and end-of-treatment (after 6 cycles of chemotherapy) PET/CT scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured at pre-treatment PET/CT. Metabolic response applying Deauville score was evaluated at interim and end-of-treatment PET/CT. Survival curves, such as progression free survival (PFS) and overall survival (OS), were calculated for the whole population. Fifty-eight (66%) patients had sarcopenia at baseline and sarcopenia rate increased at interim scan with 68 (77%) cases and at end-of-treatment scan with 73 (83%) cases. Muscular areas (SMA and SMI) declined significantly during the treatment (p < 0.001), decreasing from baseline by 5% and 7% at interim and end-of-treatment evaluation, respectively. Instead, VAT, SAT, IMAT, and TAT increased significantly over this time (p < 0.001). Sarcopenia was significantly related with comprehensive geriatric assessment. PET/CT response at interim and end-of-treatment, MTV, TLG, and baseline sarcopenia were independent prognostic factors for PFS. Instead, metabolic response at interim and end-of-treatment PET, baseline sarcopenia, ΔSMI at interim, and ΔSMI at end-of-treatment for OS were independent prognostic factors. [ABSTRACT FROM AUTHOR]