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Immuno-PET/CT imaging, a branch of molecular imaging, can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is a pan-cancer biomarker and plays a crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop and translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use. Methods: Two sdAbs (i.e., His-tagged T4 and His-tag-free RT4) are recombinantly expressed in Chinese hamster ovary cells. The purities and binding kinetics are determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, high-performance liquid chromatography, and surface plasmon resonance assays. The AlF restrained complexing agent (RESCA) method is applied to develop 18 F-labeled sdAb tracers ([ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4), followed by thorough preclinical imaging and blocking studies on tumor-bearing mice and a pilot clinical trial evaluating the clinical imaging safety and feasibility of [ 18 F]AlF-RESCA-T4 immuno-PET/CT. Results: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical imaging in the T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) of [ 18 F]AlF-RESCA-T4 (11.13 ± 1.53, n = 4) and [ 18 F]AlF-RESCA-RT4 (8.83 ± 1.22, n = 4), which were significantly reduced by coinjection of unlabeled T4 and RT4 in blocking studies. The His-tag removal strategy further optimized the probe's in vivo pharmacokinetics and reduced renal radioactivity accumulation without significantly decreasing tumor uptake. In a pilot clinical trial, [ 18 F]AlF-RESCA-T4 immuno-PET/CT showed promising potency in annotating Trop2 expression and differentiating tumors from inflammatory diseases such as tuberculosis. Conclusion: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 can specifically annotate Trop2 expression. Clinical [ 18 F]AlF-RESCA-T4 immuno-PET/CT imaging can screen patients for Trop2-targeted therapies and differentiate lung inflammation from cancer., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: For several years, oncological positron emission tomography (PET) has developed beyond 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG). This umbrella review of meta-analyses aims to provide up-to-date, comprehensive, high-level evidence to support appropriate referral for a specific radiopharmaceutical PET/computed tomography (CT) or PET/magnetic resonance (MR) in the diagnosis and staging of solid cancers other than brain malignancies., Methods: We performed a systematic literature search on the PubMed/MEDLINE and EMBASE databases for meta-analyses assessing the accuracy of PET/CT and/or PET/MRI with [ 18 F]FDG, somatostatin- receptor-targeting 68 Ga-DOTA-peptides, 18 F-labelled dihydroxyphenylalanine ([ 18 F]DOPA), prostate-specific membrane antigen (PSMA)-targeted radioligands, and fibroblast activation protein inhibitors (FAPI) in the diagnosis/disease characterisation and staging of solid cancers other than brain tumours., Results: The literature search yielded 449 scientific articles. After screening titles and abstracts and applying inclusion and exclusion criteria, we selected 173 meta-analyses to assess the strength of evidence. One article was selected from references. Sixty-four meta-analyses were finally considered. The current evidence corroborates the role of [ 18 F]FDG as the main player in molecular imaging; PSMA tracers are useful in staging and re-staging prostate cancer; somatostatin-targeting peptides (e.g. [ 68 Ga]Ga- DOTA-TOC and -TATE) or [ 18 F]DOPA are valuable in neuroendocrine tumours (NETs). FAPI has emerged in gastric cancer assessment. According to search and selection criteria, no satisfactory meta-analysis was selected for the diagnosis/detection of oesophageal cancer, the diagnosis/detection and N staging of small cell lung cancer and hepatic cell carcinoma, the diagnosis/detection and M staging of melanoma and Merkel cell carcinoma, cervical, vulvar and penis cancers, the N and M staging of lung and gastroenteropancreatic NET, testicular cancer, and chondrosarcoma, and the M staging of differentiated thyroid, bladder and anal cancers., Conclusion: The comprehensive high-level evidence synthesised in the present umbrella review serves as a guiding compass for clinicians and imagers, aiding them in navigating the increasingly intricate seascape of PET examinations., Competing Interests: Declarations. Competing interests: Matteo Bauckneht reports personal fees from AAA and General Electric Healthcare, unrelated to the present work, during the past 36 months. Winette van der Graaf has received institutional research fees from Eli Lilly. The other authors do not report any conflict of interest., (© 2024. The Author(s).)

Background: Although many well-known factors affect the maximum standardized uptake value (SUVmax), it remains the most requested and used parameter, especially among clinicians, despite other parameters, such as the standardized uptake value corrected for lean body mass and the metabolic tumor volume, being proven to be less sensitive to the same factors, more robust, and eventually more informative. This study intends to provide robust evidence regarding the diagnostic and prognostic value of SUVmax in a large cohort of subjects with suspected malignant lung nodules imaged by [ 18 F]FDG PET/CT., Materials and Methods: We performed a retrospective analysis of patients with suspected/confirmed primary lung tumours undergoing [18F]FDG PET/CT. The sample size was 567 patients. Demographics, imaging, surgical, histological, and follow-up data were collected. SUVmax was analysed according to histology, stage, scanner, and outcome. The impact on measured values of different reconstruction protocols was assessed. All potential predictors of patients' outcome were assessed., Results: 91% cases were primary lung tumours. Lung benign nodules or metastases accounted for 5% and 4% of cases. Most patients presented with adenocarcinoma (70%) and stage I disease (51%); 144 patients relapsed and 55 died. SUVmax failed to effectively differentiate benign lesions from primary tumours or metastases. Stage I patients presented lower SUVmax. SUVmax significantly correlated with patient weight, injected [ 18 F]FDG activity, and lesion size and differed between reconstructions' protocols. Survival analyses revealed no independent prognostic significance for SUVmax in progression-free after adjusting for other variables. SUVmax correlated with overall survival, disease stage and tumour histotype., Conclusion: Our study confirms that SUVmax, though widely employed, present relevant limitations in discriminating between benign lesion and lung cancer, in classifying cancer histotypes, and in predicting patient outcomes independently. Known influencing factors significantly impact on numerical values, thus SUV values should be regarded with caution in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The Ethics Committee of IRCCS Humanitas Research Hospital approved the study (approval number 3/18, on 17 April 2018, protocol ADVIMAG-Thorax). Consent to participate: A specific informed consent was waived because of the observational and retrospective study design. Competing interests: AC is editor-in-chief of EJNMMI. MK, LA and MS are in the editorial board of EJNMMI. MK and MS are section editors of the Artificial intelligence, machine learning and radiomics section of Cancer Imaging. AC reports personal fees from AmGen, General Electric Healthcare, Novartis, Sirtex, and Telix, all outside the submitted work. All other authors did not report competing interest., (© 2024. The Author(s).)

Purpose: Sentinel lymph node biopsy (SLNB) has been recognized as "the gold standard" for axillary staging in early breast cancer patients with clinically negative lymph nodes, resulting in significant morbidity decrease and quality of life improvement. This study aims to validate the performance of a newly developed handheld portable gamma camera (PGC) produced by Imagensys (Italy), in detecting and locating sentinel lymph nodes (SLNs) during the preoperative and intraoperative phases in breast cancer patients compared to conventional lymphoscintigraphy., Methods: Adult female patients with histologically confirmed breast cancer, candidates for surgery and SLNB, were prospectively enrolled in this open-label, pre-marketing clinical trial. All patients underwent pre- operative assessment using both the PGC and conventional lymphoscintigraphy. The performance of the two devices was compared using the Poisson regression model for incidence rate ratios (IRRs). The intrinsic sensitivity of the devices was compared using the Wilcoxon Ranked Sign Test. The utility of PGC during intra-operative procedures was also evaluated. The manoeuvrability of the devices was evaluated using operator-satisfaction questioner., Results: Sixty-eight patients (median age 50 years, BMI 21.4) were enrolled, including two patients with bilateral breast cancer, who underwent SLNB on both axillae. The PGC demonstrated superior preoperative lymph node detection rate (IRR 8.01, 95% CI 6.11-10.50; p < 0.0001) and intrinsic device sensitivity (mean counts per second 409 ± 286 vs. 255 ± 1173 for conventional device, p = 0.0003) compared to the conventional gamma camera. Intra-operative assessment with PGC was performed in 62 patients and no additional lymph nodes were visualised. However, the conventional gamma camera demonstrated superior manoeuvrability (p < 0.0001)., Conclusion: The PGC handheld gamma camera showed promising results for preoperative SLN assessment in patients with breast cancer. The limited manoeuvrability may be related to the operator's experience leading to higher inter-operator variability. Appropriate training and frequent use of nuclear medicine and surgical equipment could overcome this limitation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recently, radiomics has emerged as a possible image-derived biomarker, predominantly stemming from retrospective analyses. We aimed to prospectively assess the predictive role of [ 18 F]FDG-PET radiomics in breast cancer (BC)., Methods: Patients affected by stage I-III BC eligible for neoadjuvant chemotherapy (NAC) staged with [ 18 F]FDG-PET/CT were prospectively enrolled. The pathological response to NAC was assessed on surgical specimens. From each primary breast lesion, we extracted radiomic PET features and their predictive role with respect to pCR was assessed. Uni- and multivariate statistics were used for inference; principal component analysis (PCA) was used for dimensionality reduction., Results: We analysed 93 patients (53 HER2+ and 40 triple-negative (TNBC)). pCR was achieved in 44/93 cases (24/53 HER2+ and 20/40 TNBC). Age, molecular subtype, Ki67 percent, and stage could not predict pCR in multivariate analysis. In univariate analysis, 10 radiomic indices resulted in p < 0.1. We found that 3/22 radiomic principal components were discriminative for pCR. Using a cross-validation approach, radiomic principal components failed to discriminate pCR groups but predicted the stage (mean accuracy = 0.79 ± 0.08)., Conclusions: This study shows the potential of PET radiomics for staging purposes in BC; the possible role of radiomics in predicting the pCR response to NAC in BC needs to be further investigated.

Background/Objectives: Disease recurrence and resistance to radioiodine (RAI) therapy are major challenges in the management of differentiated thyroid cancer (DTC). In particular, the TENIS (Thyroglobulin Elevated Negative Iodine Scintigraphy) syndrome, characterised by elevated thyroglobulin (Tg) serum levels in addition to a negative radioiodine whole body scan (WBS), complicates disease monitoring and treatment decisions. Conventional imaging techniques often fail to detect disease in WBS-negative patients with rising Tg levels, leading to limitations in therapeutic intervention. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of nuclear imaging modalities in detecting disease recurrence in patients with the TENIS syndrome and to provide insights to guide therapeutic approaches in this complex clinical scenario. Methods : A comprehensive search of PubMed/MEDLINE and EMBASE databases up to March 2024 was performed according to PRISMA guidelines. Eligible studies were selected, and quality assessment was performed with the QUADAS-2 tool. For each study, relevant data were extracted and synthesised. A meta-analysis of the diagnostic accuracy of [ 18 F]FDG PET/CT was performed, and patient-based pooled sensitivity and specificity were calculated using a random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic. Results : Of the 538 studies initially identified, 22 were included in the systematic review, of which 18 were eligible for meta-analysis. The eligible studies, mainly focused on [ 18 F]FDG PET/CT, showed variable sensitivity and specificity for the detection of RAI-refractory thyroid cancer lesions. For [ 18 F]FDG PET/CT, pooled estimates displayed a sensitivity of 0.87 (95% CI: 0.82-0.90) and a specificity of 0.76 (95% CI: 0.61-0.86), with moderate heterogeneity between studies. Conclusions : [ 18 F]FDG PET/CT remains central in the detection of disease recurrence in patients with the TENIS syndrome. The emergence of novel radiopharmaceuticals with specific molecular targets is a promising way to overcome the limitations of [ 18 F]FDG in these patients and to open new theranostics perspectives. This review highlights the great potential of nuclear medicine in guiding therapeutic strategies for RAI-refractory thyroid cancer.

This review aims to take a journey into the transformative impact of artificial intelligence (AI) on positron emission tomography (PET) imaging. To this scope, a broad overview of AI applications in the field of nuclear medicine and a thorough exploration of deep learning (DL) implementations in cancer diagnosis and therapy through PET imaging will be presented. We firstly describe the behind-the-scenes use of AI for image generation, including acquisition (event positioning, noise reduction though time-of-flight estimation and scatter correction), reconstruction (data-driven and model-driven approaches), restoration (supervised and unsupervised methods), and motion correction. Thereafter, we outline the integration of AI into clinical practice through the applications to segmentation, detection and classification, quantification, treatment planning, dosimetry, and radiomics/radiogenomics combined to tumour biological characteristics. Thus, this review seeks to showcase the overarching transformation of the field, ultimately leading to tangible improvements in patient treatment and response assessment. Finally, limitations and ethical considerations of the AI application to PET imaging and future directions of multimodal data mining in this discipline will be briefly discussed, including pressing challenges to the adoption of AI in molecular imaging such as the access to and interoperability of huge amount of data as well as the "black-box" problem, contributing to the ongoing dialogue on the transformative potential of AI in nuclear medicine.Relevance statementAI is rapidly revolutionising the world of medicine, including the fields of radiology and nuclear medicine. In the near future, AI will be used to support healthcare professionals. These advances will lead to improvements in diagnosis, in the assessment of response to treatment, in clinical decision making and in patient management.Key points• Applying AI has the potential to enhance the entire PET imaging pipeline.• AI may support several clinical tasks in both PET diagnosis and prognosis.• Interpreting the relationships between imaging and multiomics data will heavily rely on AI., (© 2024. The Author(s).)

Aim: Unspecific bone uptake is one of the main limitations of PET imaging with some PSMA-targeting radiopharmaceuticals, especially with [ 18 F]PSMA-1007. We explored the potential association between osteoporosis and the occurrence of unspecific [ 18 F]PSMA-1007 bone uptake investigating markers which might correlate with bone mineral density., Materials and Methods: We retrospectively analyzed treatment-naïve patients with a confirmed diagnosis of prostate adenocarcinoma who underwent staging [ 18 F]PSMA-1007 positron emission tomography (PET). Qualitative image analysis was performed independently by three experienced nuclear medicine physicians. Patients were divided in two groups according to the presence/absence of unspecific bone uptake. Clinical information, blood count parameters (assessed within 3 months to the PET scan), body mass index (BMI), and bone density as estimated by computed tomography were collected. The Kruskal-Wallis and t-test were used to compare parameters., Results: We analyzed 77 patients: 29 of them (38%) had unspecific bone uptake at [ 18 F]PSMA-1007 PET, most commonly in the pelvic bones (69%) and ribs (62%). We did not find any significant difference in clinical parameters in the two groups. In patients with unspecific bone uptake, white blood cell, and neutrophil counts were significantly higher; in the same group, we observed lower values of BMI and bone density, although not statistically different., Conclusions: We observed unspecific bone uptake on [ 18 F]PSMA-1007 PET in more than 1/3 of patients. In this exploratory analysis, we found a significant correlation between blood count parameters and unspecific [ 18 F]PSMA-1007 bone uptake. We may speculate that [ 18 F]PSMA-1007 unspecific bone uptake could be associated with osteoporosis. This hypothesis needs to be further investigated in larger populations and exploring more specific markers of osteoporosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: IDH-wildtype (IDH-wt) diffuse gliomas with histological features of lower-grade gliomas (LGGs) are rare and heterogeneous primary brain tumours. [ 11 C]Methionine (MET) positron emission tomography (PET) is commonly used to evaluate glial neoplasms at diagnosis. The present study aimed to assess the prognostic value of MET PET in newly diagnosed, treatment naïve IDH-wt gliomas with histological features of LGGs., Methods: Patients with a histological diagnosis of IDH-wt LGG who underwent preoperative (< 100 days) MET PET/CT and surgery were retrospectively included. Qualitative and semi-quantitative analyses of MET PET images were performed. Progression-free survival (PFS) and overall survival (OS) were analysed by Kaplan-Meier curves. Cox proportional-hazards regression was used to test the association of imaging and clinical data to PFS and OS., Results: We included 48 patients (M:F = 25:23; median age 55). 39 lesions were positive and 9 negative at MET PET. Positive MET PET was significantly associated with shorter median PFS (15.7 months vs. not reached, p = 0.0146) and OS time (32.6 months vs. not reached, p = 0.0253). Incomplete surgical resection and higher TBR mean values were independent predictors of shorter PFS on multivariate analysis (p < 0.001 for both). Higher tumour grade and incomplete surgical resection were independent predictors of OS at multivariate analysis (p = 0.027 and p = 0.01, respectively)., Conclusion: MET PET is useful for the prognostic stratification of patients with IDH-wt glial neoplasms with histological LGGs features. Considering their huge biological heterogeneity, the combination of MET PET and molecular analyses may help to improve the prognostic accuracy in these diffuse gliomas subset and influence therapeutic choices accordingly., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The value of Prostate Specific Membrane Antigen (PSMA) in thyroid carcinoma (TC) is still unknown. We aimed to test the potential complementary role of PSMA expression and 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) uptake on PET/CT as biomarkers for TC outcome prediction., Materials and Methods: From a retrospective cohort of TC patients we selected those fulfilling the following inclusion/exclusion criteria: thyroidectomy in our Institution, available primary tumor tissue PSMA immunostaining, [ 18 F]FDG PET/CT and follow-up data. PSMA staining was visually assessed. PET/CT was considered positive in case of [ 18 F]FDG uptake higher than the background at the site of TC confirmed by cyto-/histology, and/or follow-up. Disease recurrence, radioiodine refractoriness (RAI-R) and status at last follow-up (LFU) were used as outcome endpoints., Results: We included 23 subjects. Disease recurrence occurred in 18 patients (median time 11 months, range 1-40); among these 12/18 developed RAI-R (median time 28 months, range 2-221), and 13/18 had evidence of disease at LFU. PSMA expression was negative in 6/23 cases. PET/CT was negative in 11/23 patients (7/11 experienced recurrence). PET/CT was positive in 9/12 patients showing RAI-R and 10/13 cases with evidence of disease at LFU. All patients with positive PET/CT had a positive PSMA immunostaining. Six out of 11 patients with negative PET/CT were positive at immunostaining, showing lower PSMA expression (median score of 30%, range 0-80%) than patients with positive PET/CT. The TC samples without PSMA expression belonged to patients who resulted negative also at PET/CT (3 experienced recurrence, 2 were RAI-R, and 1 had disease at LFU). Four out of 11 patients who resulted negative at PET/CT exhibited very high PSMA expression (≥ 70%) and although 3 of them experienced recurrence, none resulted RAI-R, and only 1 had persistent disease at LFU., Conclusions: Primary tumor PSMA expression and [ 18 F]FDG uptake seem to play a complementary prognostic role in TC. The majority of patients who expressed PSMA recurred. In the intermediate ATA risk class, patients with negative PSMA immunostaining recurred less than patients expressing PSMA. Additionally, although patients with a negative [ 18 F]FDG PET/CT had a favourable long-term outcome, PSMA assessment might be useful to timely identify subjects at higher risk of recurrence., (© 2023. The Author(s).)

Merkel Cell Carcinoma (MCC) is a rare primary cutaneous cancer with aggressive behaviour and poor prognosis. Although MCC cells express somatostatin receptors (SSTR), SSTR-targeted PET/CT is not routinely performed in clinical practice. In contrast, the use of [ 18 F]FDG PET/CT is more widespread and its prognostic role is well established. We present the case of an MCC patient suspected recurrence who underwent restaging with both [ 18 F]FDG and [ 68  Ga]Ga-DOTA-TOC PET/CT. [ 18 F]FDG PET/CT showed pathological uptake only in mediastinal lymph nodes, but SSTR imaging also revealed multiple liver and skeletal metastases, leading to significant disease upstaging and relevant changes in the therapeutic management., (© 2023. The Author(s).)

Adult-type diffuse gliomas are treated with a multimodality treatment approach that includes radiotherapy both in the primary setting, and in the case of progressive or recurrent disease. Radiation necrosis represents a major complication of radiotherapy. Recurrent disease and treatment-related changes are often indistinguishable using conventional imaging methods. The present systematic review aims at assessing the diagnostic role of PET imaging using different radiopharmaceuticals in differentiating radiation necrosis and disease relapse in irradiated adult-type diffuse gliomas. We conducted a comprehensive literature search using the PubMed/MEDLINE and EMBASE databases for original research studies of interest. In total, 436 articles were assessed for eligibility. Ten original papers, published between 2014 and 2022, were selected. Four articles focused on [ 18 F]FDG, seven on amino acid tracers ([ 18 F]FET n = 3 and [ 11 C]MET n = 4), one on [ 11 C]CHO, and one on [ 68 Ga]Ga-PSMA. Visual assessment, semi-quantitative methods, and radiomics were applied for image analysis. Furthermore, 2/10 papers were comparative studies investigating different radiopharmaceuticals. The present review, the first one on the topic in light of the new 2021 CNS WHO classification, highlighted the usefulness of PET imaging in distinguishing radiation necrosis and tumour recurrence, but revealed high heterogeneity among studies., Competing Interests: Prof. Chiti reports an unrestricted grant from Novartis, personal fees from AAA, Blue Earth Diagnostics and General Electric Healthcare, outside the submitted work. The other authors do not report any conflict of interest.

Background: PET with radiolabeled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [11C]methionine (MET) PET in assessing molecular features, tumor extent, and prognosis in newly diagnosed lower-grade gliomas (LGGs) surgically treated., Methods: One hundred and fifty-three patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [11C]MET PET/CT were retrospectively included. [11C]MET PET images were qualitatively and semi-quantitatively analyzed using tumor-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS., Results: Overall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [11C]MET PET, respectively. [11C]MET uptake was more common in oligodendrogliomas than IDH-mutant astrocytomas (87% vs 50% of cases, respectively). Among [11C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBRmax (3.22). In 25% of patients, PET helped to better delineate tumor margins compared to MRI only. In IDH-mutant astrocytomas, higher TBRmax values at [11C]MET PET were independent predictors of shorter PFS., Conclusions: This work highlights the role of preoperative [11C]MET PET in estimating the type of suspected LGGs, assessing tumor extent, and predicting biological behavior and prognosis of histologically confirmed LGGs. Our findings support the implementation of [11C]MET PET in routine clinical practice to better manage these neoplasms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Contrast-enhanced mammography (CEM) and contrast-enhanced magnetic resonance imaging (CE-MRI) are commonly used in the screening of breast cancer. The present systematic review aimed to summarize, critically analyse, and meta-analyse the available evidence regarding the role of CE-MRI and CEM in the early detection, diagnosis, and preoperative assessment of breast cancer., Methods: The search was performed on PubMed, Google Scholar, and Web of Science on 28 July 2021 using the following terms "breast cancer", "preoperative staging", "contrast-enhanced mammography", "contrast-enhanced spectral mammography", "contrast enhanced digital mammography", "contrast-enhanced breast magnetic resonance imaging" "CEM", "CESM", "CEDM", and "CE-MRI". We selected only those papers comparing the clinical efficacy of CEM and CE-MRI. The study quality was assessed using the QUADAS-2 criteria. The pooled sensitivities and specificity of CEM and CE-MRI were computed using a random-effects model directly from the STATA "metaprop" command. The between-study statistical heterogeneity was tested (I 2 -statistics)., Results: Nineteen studies were selected for this systematic review. Fifteen studies (1315 patients) were included in the metanalysis. Both CEM and CE-MRI detect breast lesions with a high sensitivity, without a significant difference in performance (97% and 96%, respectively)., Conclusions: Our findings confirm the potential of CEM as a supplemental screening imaging modality, even for intermediate-risk women, including females with dense breasts and a history of breast cancer.

Introduction and Aim: Diagnosis of hepatocellular carcinoma (HCC) often occurs when the disease is unresectable and therapeutic options are limited. The extent of disease and liver function according to Child-Pugh (C-P) classification are the main prognostic factors guiding clinicians in the management of HCC. The integration of albumin-bilirubin (ALBI) grade is emerging to assess liver function on account of its objectivity and reproducibility. Our aim was to investigate the value of the ALBI grade in predicting the outcome in patients treated with transarterial radioembolization (TARE)., Methods: We retrospectively enrolled patients with advanced and unresectable HCC treated with TARE in our institution. All patients underwent a preliminary dosimetric study before Yttrium-90 resin microsphere TARE. Barcelona Clinic Liver Cancer (BCLC), C-P, and ALBI scores were established at the time of TARE. Overall survival (OS), progression-free survival (PFS), and survival after TARE were assessed with the Kaplan-Meier method. Survival analyses were stratified according to ALBI grade, C-P, and BCLC classification. Univariate and multivariate Cox proportional regression models determined the association between prognostic factors and clinical outcomes., Results: In total, 72 patients were included in the study, showing an OS of 51 months. The ALBI grade identified groups of patients with different prognoses both in the whole cohort and within the C-P classes, especially between ALBI 1 and ALBI 2. This result is confirmed also within BCLC classes. In treatment naïve patients, the ALBI grade was not able to predict outcomes, whereas the presence and degree of portal vein thrombosis (PVT) significantly affected prognosis., Conclusions: The ALBI grade provided a more accurate prognostic stratification than the C-P classification in patients with intermediate and advanced HCC treated with TARE. However, the outcome of HCC is affected not only by liver function but also by disease-related characteristics, such as disease burden and degree of PVT. Including the ALBI grade in clinical guidelines may improve the management of patients affected by HCC., Competing Interests: AC: AmGen, speaker honorarium; Blue Earth Diagnostics, advisory board, speaker honorarium; Novartis, Advisory Board, speaker honorarium; Sirtex, speaker honorarium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gelardi, Rodari, Pini, Zanca, Artesani, Tosi, Chiti and Sollini.)

Introduction: The present paper aims to systematically review the literature on COVID-19 vaccine-related findings in patients undergoing PET/CT., Methods: The search algorithms included the following combination of terms: "PET" OR "positron emission tomography" AND "COVID"; "PET" OR "positron emission tomography" AND "COVID" AND "vaccination"; "PET" OR "positron emission tomography" AND "COVID", AND "autoimmune"., Results: We selected 17 articles which were assessed for quality and included in the systematic analysis. The most frequent vaccine-related signs on PET/CT were the deltoid [ 18 F]FDG uptake and axillary hypermetabolic lymph nodes, which were described in 8-71% and 7-90% of the patients, respectively. Similarly, frequency of these findings using other tracers than [ 18 F]FDG was greatly variable. This large variability was related to the variability in time elapsed between vaccination and PET/CT, and the criteria used to define positivity. In addition, vaccine-related findings were detected more frequently in young and immunocompetent patients than in elderly and immunocompromised ones., Discussion: Therefore, awareness on vaccination status (timing, patient characteristics, and concurrent therapies) and knowledge on patterns of radiopharmaceutical uptake are necessary to properly interpret PET/CT findings., Competing Interests: Conflict of interestProf. Chiti reports a fellowship grant from Sanofi, personal fees from AAA, Blue Earth Diagnostics and General Electric Healthcare, outside the submitted work. The other authors do not report any conflict of interest., (© The Author(s), under exclusive licence to Italian Association of Nuclear Medicine and Molecular Imaging 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [ 68  Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI)-have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role., Materials and Methods: The search, limited to January 1st, 2018-March 31st, 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", "FAPI", "PET/CT", "positron emission tomography", "fibroblast", "cancer-associated fibroblasts", "CAF", "molecular imaging", and "fibroblast imaging". Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA "metaprop" command. Between-study statistical heterogeneity was tested (I 2 -statistics)., Results: Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n = 2, 29 patients), abdominal malignancies (n = 6, 171 patients), various cancers (n = 2, 143 patients), and radiation treatment planning (n = 4, 56 patients) were included in the meta-analysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I 2  = 88.56% and I 2  = 97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I 2  = 89.18% and I 2  = 95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity., Conclusions: FAPI-PET appears promising, especially in imaging cancers unsuitable for [ 18 F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its role, specifically to identify cancer types, non-oncological diseases, and clinical settings for its applications., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fragmented data exist on the emotional and psychological distress generated by hospital admission during the pandemic in specific populations of patients, and no data exists on patients scheduled for surgery. The aim of this multicentre nationwide prospective cross-sectional survey was to evaluate the impact of pandemic on emotional status and fear of SARS-CoV-2 contagion in a cohort of elective surgical patients in Italy, scheduled for surgery during the COVID-19 pandemic., Results: Twenty-nine Italian centres were involved in the study, for a total of 2376 patients surveyed (mean age of 58 years ± 16.61; 49.6% males). The survey consisted of 28 total closed questions, including four study outcome questions. More than half of patients had at least one chronic disease (54%), among which cardiovascular diseases were the commonest (58%). The most frequent type of surgery was abdominal (20%), under general anaesthesia (64%). Almost half of the patients (46%) declared to be frightened of going to the hospital for routine checkups; 55% to be afraid of getting SARS-CoV-2 infection during hospitalization and 62% were feared of being hospitalised without seeing family members. Having an oncological disease and other patient-related, centre-related or perioperative factors were independently associated with an increased risk of fear of SARS-CoV-2 infection during hospitalization and of being hospitalised without seeing family members. A previous infection due to SARS-COV-2 was associated with a reduced risk of worse emotional outcomes and fear of SARS-CoV-2 infection during hospitalization. Patients who showed the most emotionally vulnerable profile (e.g. use of sleep-inducing drugs, higher fear of surgery or anaesthesia) were at higher risk of worse emotional status towards the hospitalization during COVID-19 pandemic. Being operated in hospitals with lower surgical volume and with COVID-19 wards was associated with worse emotional status and fear of contagion., Conclusions: Additional fear and worse emotional status may be frequent in patients scheduled for elective surgery during COVID-19 pandemic. More than half of the participants to the survey were worried about not being able to receive family visits. Psychological support may be considered for patients at higher risk of psychological distress to improve perioperative wellbeing during the pandemic., (© 2021. The Author(s).)

Purpose: The present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID., Methods: We prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly., Results: In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level)., Conclusion: [18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several "target" and "non-target" tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a study of carbon dots produced via bottom-up and top-down routes, carried out through a multi-technique approach based on steady-state fluorescence and absorption, time-resolved fluorescence spectroscopy, Raman spectroscopy, infrared spectroscopy, and atomic force microscopy. Our study focuses on a side-to-side comparison of the fundamental structural and optical properties of the two families of fluorescent nanoparticles, and on their interaction pathways with mercury ions, which we use as a probe of surface emissive chromophores. Comparison between the two families of carbon dots, and between carbon dots subjected to different functionalization procedures, readily identifies a few key structural and optical properties apparently common to all types of carbon dots, but also highlights some critical differences in the optical response and in the microscopic mechanism responsible of the fluorescence. The results also provide suggestions on the most likely interaction sites of mercury ions at the surface of carbon dots and reveal details on mercury-induced fluorescence quenching that can be practically exploited to optimize sensing applications of carbon dots.

We aimed to provide an overview on research path in nuclear medicine climbing the steps of the Evidence-Based Medicine (EBM) pyramid using review of 14 subjectively selected papers out of 111 published in the Annals of Nuclear Medicine during January-December 2019. Following the structure of the EBM hierarchy, we chose at least one study for each step of the pyramid from the basis (pre-clinical research, expert opinion, case report and case series), to the middle (case-control and cohort studies, randomised controlled trials), towards the top (meta-analyses and systematic reviews). Additionally, we collected information on the promoter of each included study: investigator-initiated trials (IITs) vs industry-sponsored trials (ISTs). We found that pre-clinical studies are primarily focused on the development of novel molecular targets in cancer, with promising results. At the same time, clinical investigations deal with cardiological, neurological, infectious and oncological applications using both SPECT and PET modalities. Additionally, radionuclide therapy gained interest and is experiencing comprehensive clinical implementation. Our overview confirms the current central role of IITs as compared with ISTs. Challenges and future directions in Nuclear Medicine research are discussed.

Purpose: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) was able to demonstrate a persistent inflammatory process., Methods: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [ 18 F]FDG positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT). Whole-body [ 18 F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [ 18 F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses., Results: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46-80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [ 18 F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [ 18 F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls., Conclusion: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.

Purpose: Radium-223 was associated with high incidence of non-vertebral fractures in patients with castration-resistant prostate cancer (CRPC). However, it is still unclear whether radium-223 may induce skeletal fragility regardless of other therapies for CRPC. We aimed at evaluating the prevalence, incidence, and determinants of vertebral fractures (VFs), i.e., the most frequent complication of skeletal fragility, in CRCP patients undergoing radium-223 therapy in the real-life clinical practice., Methods: We retrospectively reviewed 49 CRPC patients with symptomatic bone metastases treated with radium-223. Patients received median number of four radium-223 doses (range: 2-6) and were followed-up for a median period of 11 months (range: 6-44). VFs were assessed by a quantitative morphometry using lateral images of spine 11C-Choline PET/CT, excluding from the analysis the vertebral bodies affected by bone metastases., Results: Before radium-223 administration, 24 patients (49%) had VFs significantly associated with duration of androgen deprivation therapy (ADT; odds ratio 1.29) and previous abiraterone therapy (odds ratio 3.80). During radium-223 therapy, incident VFs occurred in 25% of patients, in relationship with prevalent VFs (hazard ratio 6.89) and change in serum total alkaline phosphatase values (hazard ratio 0.97), whereas the correlations with ADT and abiraterone therapy were lost. Noteworthy, the risk of VFs did not correlate with the therapeutic end points of radium-223., Conclusions: This study provides a first evidence that in real-life clinical practice, radium-223 therapy may induce skeletal fragility with high risk of VFs, likely by inhibition of bone formation and independently of ADT and abiraterone therapy.

Background: Recently, evidence has accumulated that demonstrates the potential for future applications of radiomics in many clinical settings, including thoracic oncology. Methodological reasons for the immaturity of image mining (radiomics and artificial intelligence-based) studies have been identified. However, data on the influence of the composition of the research team on the quality of investigations in radiomics are lacking., Aim: This review aims to evaluate the interdisciplinarity within studies on radiomics in thoracic oncology in order to assess its influence on the quality of research (QUADAS-2 score) in the image mining field., Methods: We considered for inclusion radiomics investigations with objectives relating to clinical practice in thoracic oncology. Subsequently, we interviewed the corresponding authors. The field of expertise and/or educational degree was then used to assess interdisciplinarity. Subsequently, all studies were evaluated applying the QUADAS-2 score and assigned to a research phase from 0 to IV., Results: Overall, 27 studies were included. The study quality according to the QUADAS-2 score was low (score ≤5) in 8, moderate (=6) in 12, and high (≥7) in 7 papers. An interdisciplinary team (at least 3 different expertise categories) was involved in half of the papers without any type of validation and in all papers with independent validation. Clinicians were not involved in phase 0 studies while they contributed to all papers classified as phase I and to 4/5 papers classified as phase II with independent validation., Conclusions: The composition of the research team influences the quality of investigations in radiomics. Also, growth in interdisciplinarity appears to reflect research development from the early phase to a more mature, clinically oriented stage of investigation., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)