Search

Rational: To validate a population-based input function (PBIF) model that alleviates the need for scanning since injection time in dynamic whole-body (WBdyn) PET. Methods: Thirty-seven patients with suspected/known well-differentiated neuroendocrine tumors were included (GAPETNET trial NTC03576040). All WBdyn 68Ga-DOTATOC-PET/CT acquisitions were performed on a digital PET system (one heart-centered 6 min-step followed by nine WB-passes). The PBIF model was built from 20 image-derived input functions (IDIFs) obtained from a respective number of patients' WBdyn exams using an automated left-ventricle segmentation tool. All IDIF peaks were aligned to the median time-to-peak, normalized to patient weight and administrated activity, and then fitted to an exponential model function. PBIF was then applied to 17 independent patient studies by scaling it to match the respective IDIF section at 20-55 min post-injection time windows corresponding to WB-passes 3-7. The ratio of area under the curves (AUCs) of IDIFs and PBIF3-7 were compared using a Bland--Altman analysis (mean bias ± SD). The Patlakestimated mean Ki for physiological uptake (Ki-liver and Ki-spleen) and tumor lesions (Ki-tumor) using either IDIF or PBIF were also compared. Results: The mean AUC ratio (PBIF/IDIF) was 0.98 ± 0.06. The mean Ki bias between PBIF3-7 and IDIF was -2.6 ± 6.2% (confidence interval, CI: -5.8; 0.6). For Ki-spleen and Ki-tumor, low relative bias with low SD were found [4.65 ± 7.59% (CI: 0.26; 9.03) and 3.70 ± 8.29% (CI: -1.09; 8.49) respectively]. For Ki-liver analysis, relative bias and SD were slightly higher [7.43 ± 13.13% (CI: -0.15; 15.01)]. Conclusion: Our study showed that the PBIF approach allows for reduction in WBdyn DOTATOC-PET/CT acquisition times with a minimum gain of 20 min. [ABSTRACT FROM AUTHOR]

Simple Summary: Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma have potential to serve as an alternative for non-invasive Gleason score characterization, for the prediction of biochemical recurrence and to differentiate benign from malignant increased tracer uptake. However, prior to their implementation in clinical practice, additional, clinically relevant studies performed according to recently published guidelines and checklists, offering full transparency, including large enough datasets as well as external validation, are mandatory. Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk. Methods: Patients with SLE (n = 77) and healthy controls (HCs) (n = 27) underwent assessments of arterial stiffness, vascular wall inflammation, and coronary atherosclerosis burden with cardio‐ankle vascular index (CAVI); fluorodeoxyglucose–positron emission tomography/computed tomography (CT) (target‐to‐background ratio [TBR]); and coronary CT angiography. Whole blood bulk RNA sequencing was performed in a subset of study participants (HC n = 10, SLE n = 20). In a partially overlapping subset (HC n = 24, SLE n = 64), serum inflammatory protein biomarkers were quantified with an Olink platform. Results: CAVI, TBR, and noncalcified coronary plaque burden (NCB) were increased in patients with SLE compared to HCs. When comparing patients with SLE with high CAVI scores to those with low CAVI scores or to HCs, there was a down‐regulation of genes in pathways involved in the cell cycle and differentially regulated pathways related to metabolism. Distinct serum proteins associated with increased CAVI (CCL23, colony‐stimulating factor 1, latency‐activating peptide transforming growth factor β1, interleukin 33 [IL‐33], CD8A, and IL‐12B), NCB (monocyte chemotactic protein 4 and FMS‐like tyrosine kinase 3 ligand [Flt3L]), and TBR (CD5, IL‐1α, AXIN1, cystatin D [CST5], and tumor necrosis factor receptor superfamily 9; P < 0.05). Conclusion: Blood gene expression patterns and serum proteins that associate with worse vascular phenotypes suggest dysregulated immune and metabolic pathways linked to premature CVD. Cytokines and chemokines identified in associations with arterial stiffness, inflammation, and NCB in SLE may allow for characterization of new CVD biomarkers in lupus. [ABSTRACT FROM AUTHOR]

Acne scarring is a common sequela of acne vulgaris, which seriously affects facial esthetics. The treatment options for acne scars vary depending on the development stage, color, type, and location of scarring. The objective and precise assessment of acne scars is a prerequisite for treatment, and it is also an important means of monitoring the treatment effect. The traditional methods to evaluate the types and severity grade of acne scars are primarily based on subjective assessment by physicians, which lacks objectivity and accuracy. Novel noninvasive skin imaging techniques, such as skin surface imaging analysis systems, dermoscopy, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), and multiphoton tomography (MPT), provide new tools for the rapid and objective assessment of acne scars. This article reviews the progress of skin imaging techniques in the diagnosis, classification, and efficacy evaluation of acne scars. [ABSTRACT FROM AUTHOR]

Introduction: In multiplexed positron emission tomography (mPET) imaging, physiological and pathological information from different radiotracers can be observed simultaneously in a single dynamic PET scan. The separation of mPET signals within a single PET scan is challenging due to the fact that the PET scanner measures the sum of the PET signals of all the tracers. The conventional multitracer compartment modeling (MTCM) method requires staggered injections and assumes that the arterial input functions (AIFs) of each tracer are known. Methods: In this work, we propose a deep learning-based method to separate triple-tracer PET images without explicitly knowing the AIFs. A dynamic tripletracer noisy MLEM reconstruction was used as the network input, and dynamic single-tracer noisy MLEM reconstructions were used as training labels. Results: A simulation study was performed to evaluate the performance of the proposed framework on triple-tracer ([18F]FDG+82Rb+[94mTc]sestamibi) PET myocardial imaging. The results show that the proposed methodology substantially reduced the noise level compared to the results obtained from single-tracer imaging. Additionally, it achieved lower bias and standard deviation in the separated single-tracer images compared to the MTCM-based method at both the voxel and region of interest (ROI) levels. Discussion: As compared to MTCM separation, the proposed method uses spatiotemporal information for separation, which improves the separation performance at both the voxel and ROI levels. The simulation study also demonstrates the feasibility and potential of the proposed DL-based method for the application to pre-clinical and clinical studies. [ABSTRACT FROM AUTHOR]

Positron Emission Tomography (PET) is a powerful medical imaging technique widely used for detection and monitoring of disease. However, PET imaging can be adversely affected by patient motion, leading to degraded image quality and diagnostic capability. Hence, motion gating schemes have been developed to monitor various motion sources including head motion, respiratory motion, and cardiac motion. The approaches for these techniques have commonly come in the form of hardware-driven gating and data-driven gating, where the distinguishing aspect is the use of external hardware to make motion measurements vs. deriving these measures from the data itself. The implementation of these techniques helps correct for motion artifacts and improves tracer uptake measurements. With the great impact that these methods have on the diagnostic and quantitative quality of PET images, much research has been performed in this area, and this paper outlines the various approaches that have been developed as applied to whole-body PET imaging. [ABSTRACT FROM AUTHOR]

Introduction: Islet xenotransplantation may be a therapeutic option in type 1 diabetes. Recent advances in generating genetically modified source pigs offer advantages as immune suppressants can potentially be eliminated after the transplantation. Therapy monitoring would greatly benefit from noninvasive methods for assessing the viability of transplanted islets. Peptide-based positron emission tomography (PET) targeting the glucagon-like peptide-1 receptor (GLP1R) expression on beta cells may offer a procedure that can directly be translated from an experimental setting to the clinic. The aim of this study was to establish the labeling of the GLP1R ligand [68Ga]Ga-exendin-4, to demonstrate the feasibility of imaging porcine islet xenografts in vivo and to compare signal quality for three different transplantation sites in a mouse model. Materials and methods: Mice with engrafted neonatal porcine islet cell clusters (NPICCs) under the kidney capsule, into the inguinal fold, or the lower hindlimb muscle were studied. After reaching normoglycemia, the mice were injected with [68Ga]Ga-exendin-4 for PET data acquisition. Subsequent autoradiography (AR) was used for comparing ex vivo data with in vivo uptake. Results: NPICCs in the lower right hindlimb muscle could be detected in vivo and in AR. Due to the high background in the kidney and urinary bladder, islets could not be detected in the PET data at transplantation sites close to these organs, while AR showed a clear signal for the islets in the inguinal fold. Discussion: PET with [68Ga]Ga-exendin-4 detects islets transplanted in the hindlimb muscle tissue of mice, offering the potential of longitudinal monitoring of viable porcine islets. Other sites are not suitable for in vivo imaging owing to high activity accumulation of Exendin-4 in kidney and bladder. [ABSTRACT FROM AUTHOR]

The synchronous malignant melanoma of the neck and papillary thyroid cancer is rare but severe condition. Here, we describe the case of a patient with papillary thyroid cancer and melanoma invasivum cutis. A 49-year-old man had a change on the neck at the last 3–4 months that he accidentally noticed. He had hoarse voice, was afebrile, did not sweat more than usual and feel exhausted, without rash or itching. MR examination of the neck and upper mediastinum before the surgery indicated a hyperintense focal change in the left thyroid gland which dimensions was 19·15mm and several hyperintense inhomogeneous lymph glands of the jugular chain, on the both sides, with different sizes. On the basis of the conducted analyzes, in addition to total thyroidectomy, two-sided functional dissection of the lymph nodes of the neck was performed. The pathohistological diagnosis of the left lobus was: Carcinoma papillary glandulae thyreoideae invasivum (G-I, nG-I, pT2, Lx, Vo). CT of head, neck and thorax were made, where it was noticed that the CT of the head and lungs were normal. PET/CT findings indicated that there was no rest or recurrence of the tumor. The message from this case report is that when diagnosing and treating thyroid cancer, the observed changes in the neck lymph nodes also indicate cancers of non-thyroid pathology such as malignant melanoma. [ABSTRACT FROM AUTHOR]

Aims In systemic light-chain (AL) amyloidosis, quantification of right ventricular (RV) amyloid burden has been limited and the pathogenesis of RV dysfunction is poorly understood. Using 18F-florbetapir positron emission tomography/computed tomography (PET/CT), we aimed to quantify RV amyloid; correlate RV amyloid with RV structure and function; determine the independent contributions of RV, left ventricular (LV), and lung amyloid to RV function; and associate RV amyloid with major adverse cardiac events (MACE: death, heart failure hospitalization, cardiac transplantation). Methods and results We prospectively enrolled 106 participants with AL amyloidosis (median age 62 years, 55% males) who underwent 18F-florbetapir PET/CT, magnetic resonance imaging, and echocardiography. 18F-florbetapir PET/CT identified RV amyloid in 63% of those with and 40% of those without cardiac involvement by conventional criteria. RV amyloid burden correlated with RV ejection fraction (EF), RV free wall longitudinal strain (FWLS), RV wall thickness, RV mass index, N-terminal pro-brain natriuretic peptide, troponin T, LV amyloid, and lung amyloid (each P < 0.001). In multivariable analysis, RV amyloid burden, but not LV or lung amyloid burden, predicted RV dysfunction (EF P = 0.014; FWLS P < 0.001). During a median follow-up of 28 months, RV amyloid burden predicted MACE (P < 0.001). Conclusion This study shows for the first time that 18F-florbetapir PET/CT identifies early RV amyloid in systemic AL amyloidosis prior to alterations in RV structure and function. Increasing RV amyloid on 18F-florbetapir PET/CT is associated with worse RV structure and function, predicts RV dysfunction, and predicts MACE. These results imply a central role for RV amyloid in the pathogenesis of RV dysfunction. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: This review discusses new radiotracers for diagnosing and treating thyroid cancer. It focuses on PSMA-based tracers, FAPI-based tracers, RGD-based tracers, and 18F-TFB. These tracers show promise in detecting thyroid cancer, especially in challenging cases. They offer better accuracy and help in choosing the right treatment. Further research is needed, especially on the promising 18F-TFB and FAP-targeting tracers, to improve thyroid cancer staging and treatment outcomes. Thyroid cancer poses a significant challenge in clinical management, necessitating precise diagnostic tools and treatment strategies for optimal patient outcomes. This review explores the evolving field of radiotracers in the diagnosis and management of thyroid cancer, focusing on prostate-specific membrane antigen (PSMA)-based radiotracers, fibroblast activation protein inhibitor (FAPI)-based radiotracers, Arg-Gly-Asp (RGD)-based radiotracers, and 18F-tetrafluoroborate (18F-TFB). PSMA-based radiotracers, initially developed for prostate cancer imaging, have shown promise in detecting thyroid cancer lesions; however, their detection rate is lower than 18F-FDG PET/CT. FAPI-based radiotracers, targeting fibroblast activation protein highly expressed in tumors, offer potential in the detection of lymph nodes and radioiodine-resistant metastases. RGD-based radiotracers, binding to integrin αvβ3 found on tumor cells and angiogenic blood vessels, demonstrate diagnostic accuracy in detecting radioiodine-resistant thyroid cancer metastases. 18F-TFB emerges as a promising PET tracer for imaging of lymph node metastases and recurrent DTC, offering advantages over traditional methods. Overall, these radiotracers show promise in enhancing diagnostic accuracy, patient stratification, and treatment selection in differentiated thyroid cancer, warranting further research and clinical validation. Given the promising staging capabilities of 18F-TFB and the efficacy of FAP-targeting tracers in advanced, potentially dedifferentiated cases, continued investigation in these domains is justified. [ABSTRACT FROM AUTHOR]

Kinetic modeling represents the ultimate foundations of PET quantitative imaging, a unique opportunity to better characterize the diseases or prevent the reduction of drugs development. Primarily designed for research, parametric imaging based on PET kinetic modeling may become a reality in future clinical practice, enhanced by the technical abilities of the latest generation of commercially available PET systems. In the era of precision medicine, such paradigm shift should be promoted, regardless of the PET system. In order to anticipate and stimulate this emerging clinical paradigm shift, we developed a constructor-independent software package, called PET KinetiX, allowing a faster and easier computation of parametric images from any 4D PET DICOM series, at the whole field of view level. The PET KinetiX package is currently a plug-in for Osirix DICOM viewer. The package provides a suite of five PET kinetic models: Patlak, Logan, 1-tissue compartment model, 2-tissue compartment model, and first pass blood flow. After uploading the 4D-PET DICOM series into Osirix, the image processing requires very few steps: the choice of the kinetic model and the definition of an input function. After a 2-min process, the PET parametric and error maps of the chosen model are automatically estimated voxel-wise and written in DICOM format. The software benefits from the graphical user interface of Osirix, making it user-friendly. Compared to PMOD-PKIN (version 4.4) on twelve 18F-FDG PET dynamic datasets, PET KinetiX provided an absolute bias of 0.1% (0.05–0.25) and 5.8% (3.3–12.3) for KiPatlak and Ki2TCM, respectively. Several clinical research illustrative cases acquired on different hybrid PET systems (standard or extended axial fields of view, PET/CT, and PET/MRI), with different acquisition schemes (single-bed single-pass or multi-bed multipass), are also provided. PET KinetiX is a very fast and efficient independent research software that helps molecular imaging users easily and quickly produce 3D PET parametric images from any reconstructed 4D-PET data acquired on standard or large PET systems. [ABSTRACT FROM AUTHOR]

The article focuses on psychiatric-onset dementia with Lewy bodies (DLB), which is characterized by psychiatric symptoms like depression, psychosis, and anxiety. It discusses the longitudinal changes in clinical symptoms and imaging biomarkers in a patient with depression, highlighting the diagnostic challenges and timing of biomarker use for prodromal DLB.

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: We recently established a biological classification of head and neck cancers into hot and cold tumors, which were associated with different responses to immunotherapy (a type of cancer treatment helping the immune system fight cancer). Because this classification requires a tumor biopsy, the development of a non-invasive approach, based on imaging data, would be relevant to determine this hot/cold tumor status without performing an invasive biopsy. Thus, our goal was to determine whether imaging data from computed tomography (CT) scans can distinguish hot and cold head and neck squamous cell carcinomas (HNSCCs). Using biological and clinical imaging data from two independent cohorts, we established a computational model to determine the hot/cold status from the CT scan. This non-invasive approach, based on a "virtual" biopsy, could help for the identification and monitoring of patients with HNSCC who may benefit from immunotherapy. Background: We recently developed a gene-expression-based HOT score to identify the hot/cold phenotype of head and neck squamous cell carcinomas (HNSCCs), which is associated with the response to immunotherapy. Our goal was to determine whether radiomic profiling from computed tomography (CT) scans can distinguish hot and cold HNSCC. Method: We included 113 patients from The Cancer Genome Atlas (TCGA) and 20 patients from the Groupe Hospitalier Pitié-Salpêtrière (GHPS) with HNSCC, all with available pre-treatment CT scans. The hot/cold phenotype was computed for all patients using the HOT score. The IBEX software (version 4.11.9, accessed on 30 march 2020) was used to extract radiomic features from the delineated tumor region in both datasets, and the intraclass correlation coefficient (ICC) was computed to select robust features. Machine learning classifier models were trained and tested in the TCGA dataset and validated using the area under the receiver operator characteristic curve (AUC) in the GHPS cohort. Results: A total of 144 radiomic features with an ICC >0.9 was selected. An XGBoost model including these selected features showed the best performance prediction of the hot/cold phenotype with AUC = 0.86 in the GHPS validation dataset. Conclusions and Relevance: We identified a relevant radiomic model to capture the overall hot/cold phenotype of HNSCC. This non-invasive approach could help with the identification of patients with HNSCC who may benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular cancer (ILC) has a high propensity for multiplicity, along with a high probability of incomplete surgical excision. Due to its insidious proliferative pattern, it tends to be clinically silent and radiologically elusive. We assess the performance characteristics of PEM in the detection and local staging of ILC. Methods: A retrospective study evaluated a total of 193 patients who underwent PEM examination, including 44 patients with ILC. Image analysis of PEM examinations included morphological criteria, uptake pattern, lesion to background ratio (LTB) and maximum PEM uptake value (PUV max) assessment. The findings were correlated with the histopathological results. Results: PEM showed high performance in surgical planning and detection of additional ILC lesions with sensitivity of 90.6% and specificity 82%. The mean PUV max and LTB of ILC lesions were significantly different from those of benign lesions and IDC lesions. The cutoff average LTB and PUVmax values to differentiate ILC from benign lesions were ≥ 3.3 & ≥ 2.2, respectively. Conclusions: The inclusion of PEM provides a functional image that can improve the diagnostic accuracy of the conventional studies, decreasing the rates of false results and improving the detection of multicentric ILC lesions identification and their differentiation from other benign breast lesions. Advance in knowledge: PEM is a promising new imaging technique that further improves the pretherapeutic assessment of ILC and facilitates the assessment of patients with renal impairment. [ABSTRACT FROM AUTHOR]

Simple Summary: The pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a surrogate endpoint for predicting long-term clinical benefit in breast cancer. Recently, the use of radiomic features extracted from 18F-FDG PET/CT has emerged as a promising tool for predicting treatment outcomes in various cancers. We developed and externally validated a predictive model using 18F-FDG PET-based radiomics with the least absolute shrinkage and selection operator (LASSO) logistic method for pCR following NAC in breast cancer. Our radiomic-score model demonstrated satisfactory discriminative performances in training, internal validation, and external validation cohorts. Furthermore, the integrated radiomic model incorporating human epidermal growth factor receptor 2 (HER2) status showed improved performance compared to the radiomic-score model alone in all cohorts. The newly developed radiomic-score model might enable a more accurate and personalized assessment of the tumor response to neoadjuvant chemotherapy in breast cancer. The aim of our retrospective study is to develop and externally validate an 18F-FDG PET-derived radiomics model for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 87 breast cancer patients underwent curative surgery after NAC at Soonchunhyang University Seoul Hospital and were randomly assigned to a training cohort and an internal validation cohort. Radiomic features were extracted from pretreatment PET images. A radiomic-score model was generated using the LASSO method. A combination model incorporating significant clinical variables was constructed. These models were externally validated in a separate cohort of 28 patients from Soonchunhyang University Buscheon Hospital. The model performances were assessed using area under the receiver operating characteristic (AUC). Seven radiomic features were selected to calculate the radiomic-score. Among clinical variables, human epidermal growth factor receptor 2 status was an independent predictor of pCR. The radiomic-score model achieved good discriminability, with AUCs of 0.963, 0.731, and 0.729 for the training, internal validation, and external validation cohorts, respectively. The combination model showed improved predictive performance compared to the radiomic-score model alone, with AUCs of 0.993, 0.772, and 0.906 in three cohorts, respectively. The 18F-FDG PET-derived radiomic-based model is useful for predicting pCR after NAC in breast cancer. [ABSTRACT FROM AUTHOR]

The existing deep learning-based denoising methods predicting standard-dose PET images (S-PET) from the low-dose versions (L-PET) solely rely on a single-dose level of PET images as the input of deep learning network. In this work, we exploited the prior knowledge in the form of multiple low-dose levels of PET images to estimate the S-PET images. To this end, a high-resolution ResNet architecture was utilized to predict S-PET images from 6 to 4% L-PET images. For the 6% L-PET imaging, two models were developed; the first and second models were trained using a single input of 6% L-PET and three inputs of 6%, 4%, and 2% L-PET as input to predict S-PET images, respectively. Similarly, for 4% L-PET imaging, a model was trained using a single input of 4% low-dose data, and a three-channel model was developed getting 4%, 3%, and 2% L-PET images. The performance of the four models was evaluated using structural similarity index (SSI), peak signal-to-noise ratio (PSNR), and root mean square error (RMSE) within the entire head regions and malignant lesions. The 4% multi-input model led to improved SSI and PSNR and a significant decrease in RMSE by 22.22% and 25.42% within the entire head region and malignant lesions, respectively. Furthermore, the 4% multi-input network remarkably decreased the lesions' SUVmean bias and SUVmax bias by 64.58% and 37.12% comparing to single-input network. In addition, the 6% multi-input network decreased the RMSE within the entire head region, within the lesions, lesions' SUVmean bias, and SUVmax bias by 37.5%, 39.58%, 86.99%, and 45.60%, respectively. This study demonstrated the significant benefits of using prior knowledge in the form of multiple L-PET images to predict S-PET images. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia is associated with a loss of skeletal muscle. The analysis of CT images has facilitated the measurement of such changes. Whether these measurements have prognostic value for survival in patients with advanced cancer when adjusted for inflammation has recently been questioned. Therefore, the aim of the present study was to examine if CT-derived skeletal muscle measures were related to survival, independent of how inflamed the patient is. Our results suggest that CT-derived muscle measurements do not have independent prognostic value for survival in patients with advanced cancer when the inflammatory status of the patients is considered. The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p < 0.05) and mGPS (p < 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p < 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p < 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Aims and background: Hepatocellular carcinoma (HCC), ranks as the third most prevalent malignancy contributing to cancer-related death on a global scale. Hepatocellular carcinoma is known to be the fifth most frequently diagnosed malignancy of the males while among females, it is ranked as the seventh most common malignancy. The study was conducted to detect the sensitivity of primary HCC using 18F-flourodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan. Materials and methods: This prospective study was conducted to identify the primary HCC in a sample size of 51 patients, in whom FDG PET-CT scan was performed between May 2022 and December 2022. Results: Among the cohort of 51 patients, primary HCC was detected on FDG PET-CT in 43 individuals representing true-positive cases. Conversely, FDG PET-CT was unable to detect HCC in 8 cases, representing false-negative. Out of 51 patients, 74.5% of HCC cases exhibited multifocal pattern. The maximum standardized uptake value (SUV max) of the primary malignant site ranged from 1.9 to 16.1, with a mean of 3.7 ± 2.8. The FDG PET-CT revealed abnormal sites of the uptake outside liver in 23 individuals. The research confirmed the tumor recurrence in four previously treated patients. In the conducted investigation, FDG PET-CT showed 84.3% sensitivity for the diagnosis of HCC. Conclusion: The study demonstrates that FDG PET-CT is a viable option for the detection of HCC. The sensitivity of FDG PET-CT in our population is comparable and in agreement with international data for diagnosis of HCC thereby favoring its reproducibility among geographical and ethnic groups. However, owing to the reduced ability of FDG PET-CT scan to identify well-differentiated/low-grade HCC, the routine use of FDG PET-CT scan may not be considered in cases requiring evaluation of primary disease only. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal cancers represent a major burden in oncology worldwide. As radiotherapy is a cornerstone of the treatment strategies, accurate treatment planning is necessary. Imaging modalities, such as positron emission tomography with computed tomography (PET/CT) and magnetic resonance (MRI) could improve target volume determination. This review summarizes the role of PET/CT and MRI in radiotherapy treatment planning for anal, esophageal, rectal and pancreatic cancer. Positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI) could improve accuracy in target volume determination for gastrointestinal cancers. A systematic search of the PubMed database was performed, focusing on studies published within the last 20 years. Articles were considered eligible for the review if they included patients with anal canal, esophageal, rectal or pancreatic cancer, as well as PET/CT or MRI for radiotherapy treatment planning, and if they reported interobserver variability or changes in treatment planning volume due to different imaging modalities or correlation between the imaging modality and histopathologic specimen. The search of the literature retrieved 1396 articles. We retrieved six articles from an additional search of the reference lists of related articles. Forty-one studies were included in the final review. PET/CT seems indispensable for target volume determination of pathological lymph nodes in esophageal and anal canal cancer. MRI seems appropriate for the delineation of primary tumors in the pelvis as rectal and anal canal cancer. Delineation of the target volumes for radiotherapy of pancreatic cancer remains challenging, and additional studies are needed. [ABSTRACT FROM AUTHOR]

Non-invasive diagnostic method based on radiomic features in patients with non-small cell lung cancer (NSCLC) has attracted attention. This study aimed to develop a CT image-based model for both histological typing and clinical staging of patients with NSCLC. A total of 309 NSCLC patients with 537 CT series from The Cancer Imaging Archive (TCIA) database were included in this study. All patients were randomly divided into the training set (247 patients, 425 CT series) and testing set (62 patients, 112 CT series). A total of 107 radiomic features were extracted. Four classifiers including random forest, XGBoost, support vector machine, and logistic regression were used to construct the classification model. The classification model had two output layers: histological type (adenocarcinoma, squamous cell carcinoma, and large cell) and clinical stage (I, II, and III) of NSCLC patients. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence interval (CI) were utilized to evaluate the performance of the model. Seven features were selected for inclusion in the classification model. The random forest model had the best classification ability compared with other classifiers. The AUC of the RF model for histological typing and clinical staging of NSCLC patients in the testing set was 0.700 (95% CI, 0.641–0.759) and 0.881 (95% CI, 0.842–0.920), respectively. The CT image-based radiomic feature model had good classification ability for both histological typing and clinical staging of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an old-age disease that comes in different stages and directly affects the different regions of the brain. The research into the detection of AD and its stages has new advancements in terms of single-modality and multimodality approaches. However, sustainable techniques for the detection of AD and its stages still require a greater extent of research. In this study, a multimodal image-fusion method is initially proposed for the fusion of two different modalities, i.e., PET (Positron Emission Tomography) and MRI (Magnetic Resonance Imaging). Further, the features obtained from fused and non-fused biomarkers are passed to the ensemble classifier with a Random Forest-based feature selection strategy. Three classes of Alzheimer's disease are used in this work, namely AD, MCI (Mild Cognitive Impairment) and CN (Cognitive Normal). In the resulting analysis, the Binary classifications, i.e., AD vs. CN and MCI vs. CN, attained an accuracy (Acc) of 99% in both cases. The class AD vs. MCI detection achieved an adequate accuracy (Acc) of 91%. Furthermore, the Multi Class classification, i.e., AD vs. MCI vs. CN, achieved 96% (Acc). [ABSTRACT FROM AUTHOR]

Objective: The added value of hybrid positron emission tomography is increasingly recognised in head and neck cancer. However, its potential role in salivary gland carcinomas has been scarcely investigated. Methods: A consecutive cohort of 45 salivary gland carcinoma patients who underwent pre-therapeutic hybrid positron emission tomography and surgical resection was reviewed. This study investigated whether maximum standardised uptake value correlated with tumour phenotype. Results: Tumours of high-grade disease on histology (salivary duct carcinoma, carcinoma ex pleomorphic adenoma) had higher maximum standardised uptake value (Kruskal–Wallis test, p = 0.011) than low-grade tumours (adenoid cystic carcinoma and acinic cell carcinoma). Patients with pathologically confirmed node-positive disease had significantly higher maximum standardised uptake value of the primary tumour than patients with pathologically confirmed node-negative disease (Kruskal–Wallis test, p = 0.012). Conclusion: Maximum standardised uptake value of the primary tumour may guide clinical decision-making in patients with salivary gland carcinomas, as a high maximum standardised uptake value is associated with high-grade tumour histology and the presence of lymph node metastases. Clinicians may consider more aggressive surgery for these patients. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common malignant B-cell neoplasm, with an incidence of 5.6 per 100 000 persons per year and a mean age of onset of approximately 65 years. It is an aggressive type of non-Hodgkin's lymphoma requiring urgent treatment with curative intent. Evidence-based guidelines have not been available to date. Methods: For this first international evidence-based DLBCL-specific guideline, various systematic literature searches were performed. 5 systematic reviews, 21 randomized controlled trials (RCTs), and 36 non-randomized studies were used to formulate 42 recommendations. 142 were formulated on the basis of expert consensus. All recommendations were approved in a structured consensus-finding process. Results: For staging, combined positron emission tomography and computed tomography (PET/CT) should be performed (evidence: a prospective registry study). For all patients with a new diagnosis of DLBCL and without contraindications, R-CHOP based immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) should be initiated with curative intent (evidence: RCTs). The individual treatment strategy is tailored to the patient's age and risk constellation. Once immunochemotherapy has been completed, PET/CT should be performed again to check for remission. Patients with PET-positive residual disease that is amenable to radiotherapy should be treated with consolidating irradiation (evidence: retrospective cohort study). Conclusion: This clinical practice guideline on the diagnosis, treatment, and followup of patients with DLBCL and related entities provides a standardized clinical management approach, identifies areas where improvement would be desirable, and can serve as a basis for the development of further studies. [ABSTRACT FROM AUTHOR]

Primary pulmonary Hodgkin’s lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin-Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists. [ABSTRACT FROM AUTHOR]

Background: The quality of positron emission tomography/computed tomography (PET/CT) images plays an important role in tumor detection. This imaging method often yields poor-quality images of overweight patients due to the high level of noise, originating from scattering and photon attenuation. Objectives: The point spread function (PSF) is mostly used to enhance the spatial resolution and signal-to-noise ratio (SNR); however, it is known to increase the edge artifacts. The time-of-flight (TOF) principle can reduce edge artifacts in PSF modeling and improve lesion detection, especially in the thorax. The present study aimed to assess these two new techniques by applying different reconstruction parameters. Materials and Methods: An in-house phantom with an inner diameter of 35cmwas used for the simulation of overweight patients. Lesion-to-background ratios (LBRs) of 2: 1 and 8: 1, as well as background activity concentrations of 3 and 5 kBq/cc, were considered in this study. The list-mode data were reconstructed with various reconstruction protocols, numbers of subsets, and filter sizes. Quantitative analyses, including the coefficient of variation (COV), SNR, and recovery coefficient (RC), were also carried out. Moreover, box-and-whisker plots were performed. Results: At LBR of 2: 1, by changing the protocol from ordered subset expectation maximization (OSEM) to OSEM + PSF + TOF, the median value of SNR for 13-mm lesions (37 mm) increased by 39.25% and 53.45% (42.22% and 56.21%), at background activity concentrations of 3 and 5 kBq/cc respectively. However, at LBR of 8: 1, the corresponding values were 33.22% and 48.94% (40.22% and 52.15%) at background activity concentrations of 3 and 5 kBq/cc respectively. Conclusion: The TOF protocols were strongly recommended for both background activity concentrations at LBR of 2: 1 and for the low background activity concentration at LBR of 8: 1, especially when using smaller filter sizes. Moreover, subset numbers of 18 and 24 were appropriate for all protocols. However, a smaller subset number was suitable when a low background activity concentration and a smaller filter size were applied, especially at a lower LBR. [ABSTRACT FROM AUTHOR]

Simple Summary: The definition of tumor hypoxia is important in oncology because this characteristic is linked to a poor prognosis but remains debated because there are no reference modalities. In this context, we compared PET hypoxia (FMISO) and MRI data before surgery to determine the hypoxic volume at which to increase the radiotherapy dose in head and neck cancers. To our knowledge, this is the first study showing the value of combining tumor volumes obtained via PET and MRI to define the hypoxic lesion subvolume. The quantitative MRI parameters ADC, T1 mapping, and T2 mapping showed differences between hypoxic and normoxic volumes. Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia. Thus, 16 patients were prospectively included and underwent 18F-FDG PET/CT, 18F-FMISO PET/CT, and multiparametric quantitative MRI (DCE, diffusion and relaxometry T1 and T2 techniques) in the same position before treatment. PET and MRI sub-volumes were segmented and classified as hypoxic or non-hypoxic volumes to compare quantitative MRI parameters between normoxic and hypoxic volumes. In total, 13 patients had hypoxic lesions. The Dice, Jaccard, and overlap fraction similarity indices were 0.43, 0.28, and 0.71, respectively, between the FDG PET and MRI-measured lesion volumes, showing that the FDG PET tumor volume is partially contained within the MRI tumor volume. The results showed significant differences in the parameters of SUV in FDG and FMISO PET between patients with and without measurable hypoxic lesions. The quantitative MRI parameters of ADC, T1 max mapping and T2 max mapping were different between hypoxic and normoxic subvolumes. Quantitative MRI, based on free water diffusion and T1 and T2 mapping, seems to be able to identify intra-tumoral hypoxic sub-volumes for additional radiotherapy doses. [ABSTRACT FROM AUTHOR]

Objective To investigate the success of imaging methods and the effect of preoperative findings on postoperative results in patients who underwent surgery for primary hyperparathyroidism (p-HPT). Material and Method In this study, the data of 50 consecutive patients who underwent p-HPT surgery at the General Surgery Clinic of Yuzuncu Yil University Faculty of Medicine between January 2008 and December 2010 were prospectively analyzed. During the study period, the patients' demographic data, clinical findings, preoperative and postoperative laboratory results, findings of ultrasonography, scintigraphy, and computed tomography performed for localization in the preoperative period, and surgery and pathology reports were evaluated and recorded. The obtained data were statistically analyzed. Results Musculoskeletal pain was the most common (80%) reason for the patients' presentation to the hospital. In the operated patients, the serum parathormone and calcium levels significantly decreased compared to the preoperative period (p<0.05). The rate of patients who underwent bilateral neck dissection was 30%. In the histopathological examination of the glands, adenoma lesions were detected in 88% of the patients, and the rate of those with a pathology result of parathyroid hyperplasia was 12%. In addition, 4% of the patients had ectopic pathological glands (retroesophageal, anterior mediastinum), and 4% had double adenomas. The sensitivity of ultrasonography in detecting pathological glands was calculated as 72%. However, ultrasonography did not accurately localize all ectopic (4%) and double adenoma (4%) lesions. The postoperative calcium values were similar between the patients that underwent simultaneous thyroidectomy and those that did not undergo this operation, but the parathormone values measured on the second postoperative day were significantly lower in the former. Conclusion Although ultrasonography has a high diagnostic value, it can cause mislocalization in the presence of multiple lesions with atypical localization. The risk of postoperative hypocalcemia increases as surgical exploration increases. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common primary malignant bone tumor in adolescents and children and prone to develop lung metastasis. Its prognosis has been virtually unimproved over the last few decades, especially in patients with metastases, who suffer from a dismal survival. Recently, increasing attention has been devoted to monocarboxylate transporters-related (MCTs) metabolic reprogramming. However, the role of MCT1 and MCT4 in osteosarcoma progression and the underlying mechanisms remain to be further elucidated. Methods: In this study, we established MCT1 and/or MCT4 knockout cell lines by CRISPR/Cas9 genome editing technology. Then, we assessed glycolysis and oxidative phosphorylation capacities by measuring lactate flux and oxygen consumption. We also performed flowcytometry to test circulating tumor cells and PET/CT to evaluate glucose uptake. Results: MCT1 was found to be involved in both glycolysis and oxidative respiration due to its ability to transport lactate in both directions. MCT1 inhibition significantly reduced circulating tumor cells and distant metastases partially by increasing oxidative stress. MCT4 was primarily related to glycolysis and responsible for lactate export when the concentration of extracellular lactate was high. MCT4 inhibition dramatically suppressed cell proliferation in vitro and impaired tumor growth with reduction of glucose uptake in vivo. Conclusions: Our results demonstrate the functional heterogeneity and redundancy of MCT1 and MCT4 in glucose metabolism and tumor progression in osteosarcoma. Thus, combined inhibition of MCT1 and MCT4 may be a promising therapeutic strategy for treating tumors expressing both transporters. [ABSTRACT FROM AUTHOR]

Simple Summary: Today, modern imaging techniques can predict advanced prostate cancer with a very high level of certainty. We conducted a prospective observational study of patients undergoing radical prostatectomy for prostate cancer without a prior biopsy. We saw that all patients with elevated PSA levels, a suspicious digital rectal examination, and a high likelihood of prostate cancer on preoperative mpMRI and PSMA-PET imaging were diagnosed with clinically significant prostate cancer. In fact, applying the inclusion criteria of our study, most patients were diagnosed with highly aggressive and locally advanced prostate cancer. In conclusion, we show that in highly selected cases, surgery for prostate cancer is an option. Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The patients were divided into three groups. Group 1 included 27 patients with: (i) suspicious digital rectal examination, (ii) PSA ≥ 10 ng/mL, (iii) PI-RADS 4/5 on mpMRI, and (iv) high suspicion of PCa on PSMA-PET. Group 2 included six patients who fulfilled criteria i, ii, and iii but did not undergo PSMA-PET imaging. Group 3 included 17 patients with at least one clinical (i or ii) and one imaging (iii or iv) criterion. All of the patients were diagnosed with PCa. Comparison of Group 1 and 2 versus Group 3 showed a significantly higher ratio of locally advanced PCa for Groups 1 and 2 compared to Group 3 (60.6% versus 11.8%, p = 0.005, respectively). Similarly, these patients displayed a significantly higher ratio of aggressive PCa (ISUP grade > 2: 66.7% versus 23.5%, p = 0.027, respectively) and tumor infiltration (median tumor infiltration: 32.5% vs. 15%, p = 0.001, respectively) in the final specimen compared to Group 3. In conclusion, we have shown that radical prostatectomy without prior biopsy is safe in terms of the diagnosis of clinically significant PCa when proper preoperative risk stratification involving mpMRI and PSMA-PET imaging is applied. [ABSTRACT FROM AUTHOR]

Purpose: [68 Ga]Ga-FAPI-04 PET/CT has been widely used in oncology patients. The patients need to lie still for 20–30 min during scan after waiting for 60 min post-tracer injection in traditional [68 Ga]Ga-FAPI-04 PET/CT scan. This is difficult for some patients who are intolerant to prolonged horizontal positioning and waiting time. Therefore, we evaluated the diagnostic value of the images obtained in ultra-early and fast scan (5-min p.i., 30-s acquisition time) by the total-body [68 Ga]Ga-FAPI-04 PET/CT and to investigate whether they could meet the requirements of clinical diagnosis. Methods: Total-body [68 Ga]Ga-FAPI-04 PET/CT was conducted in 12 patients at the Renji Hospital. Patients underwent PET with two acquisitions: 5-min p.i. and 30-s acquisition time (ultra-early and fast imaging) and 60-min p.i. and 300-s acquisition time (traditional imaging). Mean [68 Ga]Ga-FAPI-04 injection dose was 1.85 MBq/kg. Results: Forty-four lesions were detected in 12 patients on traditional imaging. All the 44 lesions on conventional imaging could also detected by ultra-early and fast imaging. For all the 12 patients, the tumor stage did not change, as same lesions were visible for every case in both images. There was no statistically significant difference in SUVmax of lesions between ultra-early and fast imaging and traditional imaging (12.5 ± 8.7 vs 13.7 ± 8.5, P = 0.528). Background bloodpool (4.0 ± 0.6 vs 0.9 ± 0.2, P < 0.001)and liver (2.5 ± 0.7 vs 1.0 ± 0.5, P < 0.001)at traditional imaging showed a significant decrease in SUVmean compared to ultra-early and fast imaging. Conclusions: Ultra-early and fast imaging versus traditional [68 Ga]Ga-FAPI-04 imaging resulted in equivalent tumor detection and lesion uptake. Ultra-early and fast total-body [68 Ga]Ga-FAPI-04 PET/CT scan could meet clinical diagnostic requirements for patients with poor tolerant to prolonged horizontal positioning and waiting time. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study was aimed to investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) PET/CT for evaluating focal liver lesions (FLLs) with [18F]FDG non-avidity. Methods: From January 2021 to March 2022, this prospective study included 80 FLLs that were not avid on [18F]FDG PET/CT from 37 patients, then underwent [18F]FAPI PET/CT. All patients with FLL(s) with biopsy-proof or follow-up confirmation were categorized into four subgroups (20 hepatocellular carcinomas [HCCs]/5 non-HCC malignancies/4 inflammatory FLLs/8 benign noninflammatory FLLs). The diagnostic value of [18F]FAPI for detecting liver malignancy was determined by visual evaluation. Differences in the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) obtained from [18F]FAPI PET/CT among the four subgroups were analyzed by semiquantitative analysis. Results: Among the thirty-seven enrolled participants (34 males; median age 57 years, range 48–67 years), on visual evaluation, the sensitivity, specificity, and accuracy of [18F]FAPI PET for detecting liver malignancy in the patient-based analysis were 96.0% (24/25), 58.3% (7/12), and 83.8% (31/37), respectively. On semiquantitative analysis, the SUVmax and LBR of [18F]FAPI PET in liver malignancy (33 HCC lesions; 19 non-HCC malignant lesions) were significantly higher than those in 11 benign noninflammatory FLLs [HCC: SUVmax: 6.4 vs. 4.5, P = 0.017; LBR: 5.1 vs. 1.5, P = 0.003; non-HCC: SUVmax: 5.5 vs. 4.5, P = 0.008; LBR: 4.4 vs. 1.5, P = 0.042]. Notably, there was no significant difference in the SUVmax of [18F]FAPI PET between 33 HCC lesions and 17 inflammatory FLLs (6.4 vs. 8.2, P = 0.37), but the LBR of [18F]FAPI PET in HCC were significantly lower than that in inflammatory FLLs (5.1 vs. 9.1, P = 0.003). Conclusions: [18F]FAPI PET/CT shows high sensitivity in detecting HCC and non-HCC malignancy with [18F]FDG non-avidity. [18F]FAPI might be a promising radiopharmaceutical for the differential diagnosis of benign noninflammatory FLLs and liver malignancy with [18F]FDG non-avidity. [ABSTRACT FROM AUTHOR]

The authors responds to a letter about their study on the use of a long-axial field of view scanner in a combined positron-emission tomography(PET)/computed tomography for patients for radioligand therapy. They tackle the high-quality images that may be obtained using the scanner, their disagreement with issues raised about the applicability of their protocol, and the preference for an initial low-activity prostate-specific membrane antigen radioligand therapy-PET.

Purpose: The efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features. Methods: Overall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria. Results: In the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860–0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR. Conclusion: The machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment. [ABSTRACT FROM AUTHOR]

Purpose : As bone formation is associated with psoriatic arthritis (PsA), positron emission tomography (PET) using a 18F-Fluoride tracer may enable sensitive detection of disease activity. Our primary aim was to determine the feasibility of whole-body 18F-sodium fluoride PET-CT in clinically active PsA patients to depict new bone formation (as a reflection of disease activity) at peripheral joints and entheses. Our secondary aim was to describe 18F-sodium fluoride findings in the axial skeleton. Methods: Sixteen patients (female 10/16, age 50.6 ± 8.9 years) with PsA fulfilling CASPAR criteria or with a clinical diagnosis of PsA according to the treating rheumatologist and with ≥ 1 clinically active enthesitis site were included. Of each patient, a whole-body 18F-sodium fluoride PET-CT scan was performed. All scans were scored for PET-positive lesions at peripheral joints, enthesis sites and the spine. Clinical disease activity was assessed by swollen/tender joint count 44, enthesitis according to MASES and SPARCC scores. Results: Out of 1088 evaluated joints, 109 joints showed PET enhancement, mainly in the interphalangeal and metatarsal joints of the feet (14/109, 12.9%) and the distal interphalangeal joints of the hands (14/109, 12.9%). PET positivity was found at 44/464 enthesis sites, mainly at the patella tendon insertion (11/44, 25%) and quadriceps tendon insertion (10/44, 22.7%). Of the PET-positive joints and enthesis sites, respectively 18.2% and 29.5% were clinically positive; 81.8% and 70.5% of the PET-positive joints and entheses respectively were clinically asymptomatic. In 11 patients, ≥ 1 axial PET-positive lesion was observed, mainly in the cervical spine. Conclusions: New molecular bone formation was observed on 18F-sodium fluoride PET-CT scans, in all domains in which PsA disease activity can be observed, with a substantial part showing no clinical symptoms. Clinical trial registration: EudraCT: 2017-004,850-40, registered on 13 December 2017. [ABSTRACT FROM AUTHOR]

Purpose: Sentinel lymph node (SLN) biopsy is a staging procedure in the management of cutaneous malignancies of the head. The ideal radiopharmaceutical is controversial. This study aimed to compare [99mTc]Tc-tilmanocept (TcTM) with [99mTc]Tc-sulphur colloid (TcSC) and [99mTc]Tc-albumin colloid (TcAC) for SLN detection in the head and neck region. Methods: Data from 62 patients with cutaneous malignancies of the head who were injected with TcTM, TcSC, or TcAC before SLN imaging (SLN-I) and SLN excision (SLN-E) between 2012 and 2021 were retrospectively analysed. SLN-I was performed using planar lymphoscintigraphy and SPECT/CT, and a gamma probe was used for SLN-E. The SLN-I localisation rate (patients with SLNs) and degree (SLN number) and SLN-E relocalisation rate (patients with SLNs) and ratio (SLN number in SLN-E/SLN number in SLN-I) were compared between TcTM, TcSC, and TcAC. Results: TcTM showed similar SLN-I localisation rates for primaries in the anterior and posterior head region compared with TcSC (84.6% vs. 72.4%, p=0.680; both 100.0%) and TcAC (84.6% vs. 75.0%, p=1.000; both 100.0%). The SLN-I localisation degree for TcTM was higher for primaries in the anterior head region and similar for primaries in the posterior head region compared with TcSC (3.2 vs. 2.3, p=0.034; and 1.8 vs. 2.2, p=0.506) and TcAC (3.2 vs. 2.0, p=0.038; and 1.8 vs. 2.7, p=0.329). The SLN-E relocalisation rates and ratios were similar for all. Conclusion: On the basis of a limited study design that compared three different tracers in three different patient groups, TcTM showed comparable overall performance to TcSC and TcAC. [ABSTRACT FROM AUTHOR]

Purpose: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). Methods: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. Results: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). Conclusion: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS. [ABSTRACT FROM AUTHOR]

Introduction: Zika virus (ZIKV) is a neurotropic human pathogen that causes neuroinflammation, whose hallmark is elevated translocator protein (TSPO) expression in the brain. This study investigates ZIKV-associated changes in adult brain TSPO expression, evaluates the effectiveness of TSPO radioligands in detecting TSPO expression, and identifies cells that drive brain TSPO expression in a mouse infection model. Methods: The interferon-deficient AG129 mouse infected with ZIKV was used as neuroinflammation model. TSPO expression was evaluated by tissue immunostaining. TSPO radioligands, [3H]PK11195 and [18F]FEPPA, were used for in vitro and ex vivo detection of TSPO in infected brains. [18F]FEPPA-PET was used for in vivo detection of TSPO expression. Cell subsets that contribute to TSPO expression were identified by flow cytometry. Results: Brain TSPO expression increased with ZIKV disease severity. This increase was contributed by TSPO-positive microglia and infiltrating monocytes; and by influx of TSPO-expressing immune cells into the brain. [3H]PK11195 and [18F]FEPPA distinguish ZIKV-infected brains from normal controls in vitro and ex vivo. [18F]FEPPA brain uptake by PET imaging correlated with disease severity and neuroinflammation. However, TSPO expression by immune cells contributed to significant blood pool [18F]FEPPA activity which could confound [18F]FEPPA-PET imaging results. Conclusions: TSPO is a biologically relevant imaging target for ZIKV neuroinflammation. Brain [18F]FEPPA uptake can be a surrogate marker for ZIKV disease and may be a potential PET imaging marker for ZIKV-induced neuroinflammation. Future TSPO-PET/SPECT studies on viral neuroinflammation and related encephalitis should assess the contribution of immune cells on TSPO expression and employ appropriate image correction methods to subtract blood pool activity. [ABSTRACT FROM AUTHOR]

Purpose: [68Ga]Ga-FAPI PET/CT has been widely used in clinical diagnosis and radiopharmaceutical therapy. In this study, tumor-to-blood ratio (TBR) was evaluated as a powerful tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as an effective index for tumors with high FAP expression in theranostics. Methods: Nine patients with pancreatic cancer underwent a 60-min dynamic PET/CT scan by total-body PET/CT (with a long AFOV of 194 cm) after injection of [68Ga]Ga-FAPI-04. After dynamic PET/CT scan, three patients received chemotherapy and underwent the second dynamic scan to evaluate treatment response. Time-activity curves (TACs) were obtained by drawing regions of interest for primary pancreatic lesions and metastatic lesions. The lesion TACs were fitted using four compartment models by the software PMOD PKIN kinetic modeling. The preferred pharmacokinetic model for [68Ga]Ga-FAPI-04 was evaluated based on the Akaike information criterion. The correlations between simplified methods for quantification of [68Ga]Ga-FAPI-04 (SUVs; tumor-to-blood ratios [TBRs]) and the total distribution volume (Vt) estimates obtained from pharmacokinetic analysis were calculated. Results: In total, 9 primary lesions and 25 metastatic lesions were evaluated. The reversible two-tissue compartment model (2TCM) was the most appropriate model among the four compartment models. The total distribution volume Vt values derived from 2TCM varied significantly in pathological lesions and background regions. A strong positive correlation was observed between TBRmean and Vt from the 2TCM model in pathological lesions (R2=0.92, P<0.001). The relative difference range for TBRmean was 2.1% compared to the reduction rate of Vt in the patients who were treated with chemotherapy. Conclusions: A strong positive correlation was observed between TBRmean and Vt for [68Ga]Ga-FAPI-04. TBRmean reflects FAP receptor density better than SUVmean and SUVmax, and would be the preferred measurement tool for semiquantitative assessment of [68Ga]Ga-FAPI-04 tumor uptake and as a means for evaluating treatment response. [ABSTRACT FROM AUTHOR]

Purpose: Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc receptor (FcRn)–mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS-modified equivalent, VIR-7831-WT, in cynomolgus monkeys. Methods: 89Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on the respiratory tract, and a physiologically based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values. Results: SUVmean uptake in the pulmonary bronchi for 89Zr-VIR-7831 was statistically higher than for 89Zr-VIR-7831-WT at days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively) and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUVmean uptake ratio for both mAbs was 0.25 on day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31 and 0.55, respectively. Radiomics analysis showed VIR-7831 had mean-centralized PET SUV distribution in the lung and liver, indicating more uniform uptake than VIR-7831-WT. Conclusion: The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89Zr label sheds light on the sites of antibody catabolism. [ABSTRACT FROM AUTHOR]

Purpose: To assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI). Methods: Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months. Results: The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%. Conclusions: [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling. [ABSTRACT FROM AUTHOR]

Purpose: Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8+ T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8+ cells could provide a critical biomarker for new CIT agents. However, existing 89Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging. Methods: To this end, we discovered and developed a 13-kDa single-domain antibody (VHH5v2) against human CD8 to enable high-quality, same-day imaging with a reduced radiation burden. To enable sensitive and rapid imaging, we employed a site-specific conjugation strategy to introduce an 18F radiolabel to the VHH. Results: The anti-CD8 VHH, VHH5v2, demonstrated binding to a membrane distal epitope of human CD8 with a binding affinity (KD) of 500 pM. Subsequent imaging experiments in several xenografts that express varying levels of CD8 demonstrated rapid tumor uptake and fast clearance from the blood. High-quality images were obtained within 1 h post-injection and could quantitatively differentiate the tumor models based on CD8 expression level. Conclusion: Our work reveals the potential of this anti-human CD8 VHH [18F]F-VHH5v2 to enable rapid and specific imaging of CD8+ cells in the clinic. [ABSTRACT FROM AUTHOR]

Purpose: The PET scanners with long axial field of view (AFOV) having ~ 20 times higher sensitivity than conventional scanners provide new opportunities for enhanced parametric imaging but suffer from the dramatically increased volume and complexity of dynamic data. This study reconstructed a high-quality direct Patlak Ki image from five-frame sinograms without input function by a deep learning framework based on DeepPET to explore the potential of artificial intelligence reducing the acquisition time and the dependence of input function in parametric imaging. Methods: This study was implemented on a large AFOV PET/CT scanner (Biograph Vision Quadra) and twenty patients were recruited with 18F-fluorodeoxyglucose (18F-FDG) dynamic scans. During training and testing of the proposed deep learning framework, the last five-frame (25 min, 40–65 min post-injection) sinograms were set as input and the reconstructed Patlak Ki images by a nested EM algorithm on the vendor were set as ground truth. To evaluate the image quality of predicted Ki images, mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) were calculated. Meanwhile, a linear regression process was applied between predicted and true Ki means on avid malignant lesions and tumor volume of interests (VOIs). Results: In the testing phase, the proposed method achieved excellent MSE of less than 0.03%, high SSIM, and PSNR of ~ 0.98 and ~ 38 dB, respectively. Moreover, there was a high correlation (DeepPET: R 2 = 0.73, self-attention DeepPET: R 2 =0.82) between predicted Ki and traditionally reconstructed Patlak Ki means over eleven lesions. Conclusions: The results show that the deep learning–based method produced high-quality parametric images from small frames of projection data without input function. It has much potential to address the dilemma of the long scan time and dependency on input function that still hamper the clinical translation of dynamic PET. [ABSTRACT FROM AUTHOR]