ML Models Built Using Clinical Parameters and Radiomic Features Extracted from 18F-Choline PET/CT for the Prediction of Biochemical Recurrence after Metastasis-Directed Therapy in Patients with Oligometastatic Prostate Cancer.

Oligometastatic patients at [18F]F-Fluorocholine (18F-choline) PET/CT may be treated with metastasis-directed therapy (MDT). The aim of this study was to combine radiomic parameters extracted from 18F-choline PET/CT and clinical data to build machine learning (ML) models able to predict MDT efficacy. METHODS: Oligorecurrent patients (≤5 lesions) at 18F-choline PET/CT and treated with MDT were collected. A per-patient and per-lesion analysis was performed, using 2-year biochemical recurrence (BCR) after MDT as the standard of reference. Clinical parameters and radiomic features (RFts) extracted from 18F-choline PET/CT were used for training five ML Models for both CT and PET images. The performance metrics were calculated (i.e., Area Under the Curve-AUC; Classification Accuracy-CA). RESULTS: A total of 46 metastases were selected and segmented in 29 patients. BCR after MDT occurred in 20 (69%) patients after 2 years of follow-up. In total, 73 and 33 robust RFTs were selected from CT and PET datasets, respectively. PET ML Models showed better performances than CT Models for discriminating BCR after MDT, with Stochastic Gradient Descent (SGD) being the best model (AUC = 0.95; CA = 0.90). CONCLUSION: ML Models built using clinical parameters and CT and PET RFts extracted via 18F-choline PET/CT can accurately predict BCR after MDT in oligorecurrent PCa patients. If validated externally, ML Models could improve the selection of oligorecurrent PCa patients for treatment with MDT.

[18F]FDG PET-TC radiomics and machine learning in the evaluation of prostate incidental uptake.

AIM: To evaluate the relevance of incidental prostate [18F]FDG uptake (IPU) and to explore the potential of radiomics and machine learning (ML) to predict prostate cancer (PCa). METHODS: We retrieved [18F]FDG PET/CT scans with evidence of IPU performed in two institutions between 2015 and 2021. Patients were divided into PCa and non-PCa, according to the biopsy. Clinical and PET/CT-derived information (comprehensive of radiomic analysis) were acquired. Five ML models were developed and their performance in discriminating PCa vs non-PCa IPU was evaluated. Radiomic analysis was investigated to predict ISUP Grade. RESULTS: Overall, 56 IPU were identified and 31 patients performed prostate biopsy. Eighteen of those were diagnosed as PCa. Only PSA and radiomic features (eight from CT and nine from PET images, respectively) showed statistically significant difference between PCa and non-PCa patients. Eight features were found to be robust between the two institutions. CT-based ML models showed good performance, especially in terms of negative predictive value (NPV 0.733-0.867). PET-derived ML models results were less accurate except the Random Forest model (NPV = 0.933). Radiomics could not accurately predict ISUP grade. CONCLUSIONS: Paired with PSA, radiomic analysis seems to be promising to discriminate PCa/non-PCa IPU. ML could be a useful tool to identify non-PCa IPU, avoiding further investigations.

PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?

BACKGROUND: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. RESULTS: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients' prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA-/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view.

68Ga-PSMA-11 PET/CT in Bilateral Clear Cell Renal Cell Carcinoma: an Intra-patient Comparison Between High and Low Grade Tumors.

Recent studies have outlined the emerging role of 68Ga-PSMA-11 PET/CT in the diagnostic algorithm of clear cell renal cell carcinoma (ccRCC). We report a unique intra-patient comparison of bilateral primary ccRCC imaged with 68Ga-PSMA-11 PET/CT. Although both tumors resulted 68Ga-PSMA-11 avid, we found a remarkable discrepancy in uptake intensity between the high grade and the low grade ccRCC. This case confirms previous evidence reporting that SUVmax on 68Ga-PSMA-11 PET/CT could be used to discriminate aggressive high grade from more indolent low grade ccRCC, due to their different endothelial expression of PSMA.

Comparison of MRI vs. [18F]FDG PET/CT for Treatment Response Evaluation of Primary Breast Cancer after Neoadjuvant Chemotherapy: Literature Review and Future Perspectives.

The purpose of this systematic review was to investigate the diagnostic accuracy of [18F]FDG PET/CT and breast MRI for primary breast cancer (BC) response assessment after neoadjuvant chemotherapy (NAC) and to evaluate future perspectives in this setting. We performed a critical review using three bibliographic databases (i.e., PubMed, Scopus, and Web of Science) for articles published up to the 6 June 2023, starting from 2012. The Quality Assessment of Diagnosis Accuracy Study (QUADAS-2) tool was adopted to evaluate the risk of bias. A total of 76 studies were identified and screened, while 14 articles were included in our systematic review after a full-text assessment. The total number of patients included was 842. Eight out of fourteen studies (57.1%) were prospective, while all except one study were conducted in a single center. In the majority of the included studies (71.4%), 3.0 Tesla (T) MRI scans were adopted. Three out of fourteen studies (21.4%) used both 1.5 and 3.0 T MRI and only two used 1.5 T. [18F]FDG was the radiotracer used in every study included. All patients accepted surgical treatment after NAC and each study used pathological complete response (pCR) as the reference standard. Some of the studies have demonstrated the superiority of [18F]FDG PET/CT, while others proved that MRI was superior to PET/CT. Recent studies indicate that PET/CT has a better specificity, while MRI has a superior sensitivity for assessing pCR in BC patients after NAC. The complementary value of the combined use of these modalities represents probably the most important tool to improve diagnostic performance in this setting. Overall, larger prospective studies, possibly randomized, are needed, hopefully evaluating PET/MR and allowing for new tools, such as radiomic parameters, to find a proper place in the setting of BC patients undergoing NAC.

Misinterpretation of an inflammatory FDG uptake in a patient treated for Hodgkin lymphoma: a case report.

Hodgkin Lymphoma (HL) is a malignancy involving lymph nodes and lymphatic system. [18F]F-FDG PET/CT (FDG-PET) imaging is routinely used for staging, to assess early chemotherapy response (interim FDG-PET), at the end of treatment (EoT FDG-PET) and for the identification of disease recurrence. We present a case of a 39-year-old man treated for HL. FDG-PET scans performed after first line therapy (both Interim PET and at the end of therapy) demonstrated a persistent and significant mediastinal FDG uptake. The patient was treated with a second line therapy but the FDG-PET uptake did not change. After board discussion a new surgical, thoracoscopy-guided biopsy was performed. Histopathology demonstrated a dense fibrous tissue with occasional chronic inflammatory infiltrates. Persistent FDG-PET positivity may suggest refractory or relapsed disease. However, occasionally, non-malignant conditions are responsible for a persistent FDG uptake, not related to primary disease. An accurate evaluation of clinical history and previous imaging exams is mandatory for clinicians and others experts to avoid misinterpretations of FDG-PET results. Nevertheless, in some cases, only a more invasive procedure, such as a biopsy, may finally lead to a definitive diagnosis.

Role of 18F-FDG PET/CT in evaluating lymph node status in patients with head and neck squamous cell carcinoma.

Objective: The presence of cervical lymph node metastases (CLNM) at diagnosis is one of the most relevant negative prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to analyse 2-deoxy-2[18F]fluoro-D-glucose (FDG) PET/CT findings for the identification of primary tumours and CLNM in a sample of patients affected by HNSCC. Moreover, a maximum standardised uptake value (SUVmax) threshold for the detection of CLNM was estimated. Clinical variables (i.e. smoking and alcohol habits), and tumour features (i.e. EBV and HPV positivity) were also evaluated in relation to FDG PET/CT findings. Methods: We retrospectively analysed patients who underwent FDG PET/CT for HNSCC staging between 2015-2020 at the University Hospital of Ferrara. All patients had cytological or histological confirmation of suspected cervical lymph nodes. Results: In total, 65 patients were enrolled (53 males, 12 females, median age 65.7 years). CLNM of patients with smoking habit had significantly higher SUVmax values than those of patients with previous smoking habit and non-smokers (p = 0.04). p16 positive HNSCC demonstrated a trend for higher SUVmax values on CLNM, in comparison to p16 negative tumours (p = 0.089). ROC curve analysis identified 5.8 as the best cut-off value of SUVmax for the detection of CLNM (AUC = 0.62, sensitivity 71.4% and specificity 72.7%). Conclusions: FDG PET/CT is a useful tool to evaluate CLNM in patients with HNSCC, particularly in those with smoking habit and p16 positive disease. A SUVmax cut-off of 5.8, combined with the use of conventional radiological investigations, may represent a useful tool in the identification of CLNM.

The Role of Molecular Imaging in Patients with Brain Metastases: A Literature Review.

Over the last several years, molecular imaging has gained a primary role in the evaluation of patients with brain metastases (BM). Therefore, the "Response Assessment in Neuro-Oncology" (RANO) group recommends amino acid radiotracers for the assessment of BM. Our review summarizes the current use of positron emission tomography (PET) radiotracers in patients with BM, ranging from present to future perspectives with new PET radiotracers, including the role of radiomics and potential theranostics approaches. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2022 were reviewed. Current evidence confirms the important role of amino acid PET radiotracers for the delineation of BM extension, for the assessment of response to therapy, and particularly for the differentiation between tumor progression and radionecrosis. The newer radiotracers explore non-invasively different biological tumor processes, although more consistent findings in larger clinical trials are necessary to confirm preliminary results. Our review illustrates the role of molecular imaging in patients with BM. Along with magnetic resonance imaging (MRI), the gold standard for diagnosis of BM, PET is a useful complementary technique for processes that otherwise cannot be obtained from anatomical MRI alone.

Oldie but Goodie: Is Technetium-99m Still a Treasure Trove of Innovation for Medicine? A Patents Analysis (2000-2022).

Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.

Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE.

Lutathera® is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera®. Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera® treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still "Lutathera orphans", and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera® outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera® will be considered and discussed to provide an updated picture of future investigations.

Relevance of Volumetric Parameters Applied to [68Ga]Ga-DOTATOC PET/CT in NET Patients Treated with PRRT.

BACKGROUND: this study aims to explore the prognostic and predictive role of volumetric parameters on [68Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [177Lu]Lu-DOTATOC alone or combined with [90Y]Y-DOTATOC. [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board. RESULTS: Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups (p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients (p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than -4.17% as well as those with post-SRETV_WB lower than 34.8 cm3 showed a longer PFS (p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS. CONCLUSIONS: our results could strengthen the importance of evaluating the burden of disease on [68Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT.

The Value of Semiquantitative Parameters Derived from 18F-FDG PET/CT for Predicting Response to Neoadjuvant Chemotherapy in a Cohort of Patients with Different Molecular Subtypes of Breast Cancer.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a strong prognostic factor in breast cancer (BC). The aim of this study was to investigate whether semiquantitative parameters derived from baseline [18F]Fluorodeoxyglucose ([18F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pCR after NAC and survival outcomes in patients affected by different molecular subtypes of BC. We retrospectively retrieved patients from the databases of two Italian hospitals (Centre A: University Hospital of Ferrara; Centre B: University of Padua) meeting the following inclusion criteria: (1) diagnosis of BC; (2) history of NAC; (3) baseline [18F]FDG PET/CT performed before the first cycle of NAC; (4) available follow-up data (response after NAC and survival information). For each [18F]FDG PET/CT scan, semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) related to the primary tumor (B), to the reference lesion for both axillary (N) and distant lymph node (DN), and to the whole-body burden of disease (WB) were evaluated. Patients enrolled were 133: 34 from centre A and 99 from centre B. Patients' molecular subtypes were: 9 luminal A, 49 luminal B, 33 luminal B + HER-2, 10 HER-2 enriched, and 32 triple negative (TNBC). Luminal A and HER-2 enriched BC patients were excluded from the analysis due to the small sample size. pCR after NAC was achieved in 47 patients (41.2%). [18F]FDG PET/CT detected the primary tumor in 98.3% of patients and lymph node metastases were more frequently detected in Luminal B subgroup. Among Luminal B patients, median SUVmean_B values were significantly higher (p = 0.027) in responders (7.06 ± 5.9) vs. non-responders (4.4 ± 2.1) to NAC. Luminal B + HER-2 non-responders showed a statistically significantly higher median MTV_B (7.3 ± 4.2 cm3 vs. 3.5 ± 2.5 cm3; p = 0.003) and TLG_B (36.5 ± 24.9 vs. 18.9 ± 17.7; p = 0.025) than responders at baseline [18F]FDG PET/CT. None of the semiquantitative parameters predicted pCR after NAC in TNBC patients. However, among TNBC patients who achieved pCR after NAC, 4 volumetric parameters (MTV_B, TLG_B, MTV_WB and TLG_WB) were significantly higher in patients dead at follow-up. If confirmed in further studies, these results could open up a widespread use of [18F]FDG PET/CT as a baseline predictor of response to NAC in luminal B and luminal B + HER-2 patients and as a prognostic tool in TNBC.

PET-Derived Radiomics and Artificial Intelligence in Breast Cancer: A Systematic Review.

Breast cancer (BC) is a heterogeneous malignancy that still represents the second cause of cancer-related death among women worldwide. Due to the heterogeneity of BC, the correct identification of valuable biomarkers able to predict tumor biology and the best treatment approaches are still far from clear. Although molecular imaging with positron emission tomography/computed tomography (PET/CT) has improved the characterization of BC, these methods are not free from drawbacks. In recent years, radiomics and artificial intelligence (AI) have been playing an important role in the detection of several features normally unseen by the human eye in medical images. The present review provides a summary of the current status of radiomics and AI in different clinical settings of BC. A systematic search of PubMed, Web of Science and Scopus was conducted, including all articles published in English that explored radiomics and AI analyses of PET/CT images in BC. Several studies have demonstrated the potential role of such new features for the staging and prognosis as well as the assessment of biological characteristics. Radiomics and AI features appear to be promising in different clinical settings of BC, although larger prospective trials are needed to confirm and to standardize this evidence.

Glucose Metabolism Modification Induced by Radioligand Therapy with [177Lu]Lu/[90Y]Y-DOTATOC in Advanced Neuroendocrine Neoplasms: A Prospective Pilot Study within FENET-2016 Trial.

[18F]F-FDG (FDG) PET is emerging as a relevant diagnostic and prognostic tool in neuroendocrine neoplasms (NENs), as a simultaneous decrease in [68Ga]Ga-DOTA peptides and increase in FDG uptake (the "flip-flop" phenomenon) occurs during the natural history of these tumors. The aim of this study was to evaluate the variations on FDG PET in NEN patients treated with two different schemes of radioligand therapy (RLT) and to correlate them with clinical−pathologic variables. A prospective evaluation of 108 lesions in 56 patients (33 males and 23 females; median age, 64.5 years) affected by NENs of various primary origins (28 pancreatic, 13 gastrointestinal, 9 bronchial, 6 unknown primary (CUP-NENs) and 1 pheochromocytoma) and grades (median Ki-67 = 9%) was performed. The patients were treated with RLT within the phase II clinical trial FENET-2016 (CTID: NCT04790708). RLT was offered for 32 patients with the MONO scheme (five cycles of [177Lu]Lu-DOTATOC) and for 24 with the DUO scheme (three cycles of [177Lu]Lu-DOTATOC alternated with two cycles of [90Y]Y-DOTATOC). Variations in terms of the ΔSUVmax of a maximum of three target lesions per patient (58 for MONO and 50 for DUO RLT) were assessed between baseline and 3 months post-RLT FDG PET. In patients with negative baseline FDG PET, the three most relevant lesions on [68Ga]Ga-DOTA-peptide PET were assessed and matched on post-RLT FDG PET, to check for any possible changes in FDG avidity. Thirty-five patients (62.5%) had at least one pathological FDG uptake at the baseline scans, but the number was reduced to 29 (52%) after RLT. In the patients treated with DUO-scheme RLT, 20 out of 50 lesions were FDG positive before therapy, whereas only 14 were confirmed after RLT (p = 0.03). Moreover, none of the 30 FDG-negative lesions showed an increased FDG uptake after RLT. The lesions of patients with pancreatic and CUP-NENs treated with the DUO scheme demonstrated a significant reduction in ΔSUVmax in comparison to those treated with MONO RLT (p = 0.03 and p = 0.04, respectively). Moreover, we found a mild positive correlation between the grading and ΔSUVmax in patients treated with the MONO scheme (r = 0.39, p < 0.02), while no evidence was detected for patients treated with the DUO scheme. Our results suggest that RLT, mostly with the DUO scheme, could be effective in changing NEN lesions' glycometabolism, in particular, in patients affected by pancreatic and CUP-NENs, regardless of their Ki-67 index. Probably, associating [90Y]Y-labelled peptides, which have high energy emission and a crossfire effect, and [177Lu]Lu ones, characterized by a longer half-life and a safer profile for organs at risk, might represent a valid option in FDG-positive NENs addressed to RLT. Further studies are needed to validate our preliminary findings. In our opinion, FDG PET/CT should represent a potent tool for fully assessing a patient's disease characteristics, both before and after RLT.

The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach.

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56-86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy.

The Role of [68Ga]PSMA PET/CT for Clinical Suspicion of Prostate Cancer in Patients with or without Previous Negative Biopsy: A Systematic Review.

The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of Science according to the PRISMA statement. Eighteen publications were selected for inclusion in this analysis. QUADAS-2 evaluation was adopted for quality analyses. [68Ga]PSMA-11 was the radiotracer of choice in 15 studies, while [68Ga]PSMA-617 was used in another 3. In 8 articles, there was a direct comparison with mpMRI. The total number of patients included was 1379, ranging from 15 to 291, with a median age of 64 years (range: 42-90). The median baseline PSA value was 12.9 ng/mL, ranging from 0.85 to 4156 ng/mL. Some studies evaluated the PSMA uptake comparing the SUVmax of suspicious lesions with the SUVmax of the normal biodistribution to find out optimal cut-off points. In addition, some studies suggested a significant association between PSA levels, PSA density, and [68Ga]PSMA PET/CT finding. [68Ga]PSMA PET/CT seems to be more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, in some trials, the combination of PSMA PET/CT and MRI improved the NPV in the detection of clinically significant prostate cancer (csPCa) than MRI alone. Our findings are limited by the small numbers of studies and patient heterogeneity. [68Ga]PSMA PET/CT is a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. Furthermore, its use combined with MRI improves sensitivity for csPCa detection and can avoid unnecessary biopsies.

Rhenium Radioisotopes for Medicine, a Focus on Production and Applications.

In recent decades, the use of alpha; pure beta; or beta/gamma emitters in oncology, endocrinology, and interventional cardiology rheumatology, has proved to be an important alternative to the most common therapeutic regimens. Among radionuclides used for therapy in nuclear medicine, two rhenium radioisotopes are of particular relevance: rhenium-186 and rhenium-188. The first is routinely produced in nuclear reactors by direct neutron activation of rhenium-186 via 185Re(n,γ)186Re nuclear reaction. Rhenium-188 is produced by the decay of the parent tungsten-188. Separation of rhenium-188 is mainly performed using a chromatographic 188W/188Re generator in which tungsten-188 is adsorbed on the alumina column, similar to the 99Mo/99mTc generator system, and the radionuclide eluted in saline solution. The application of rhenium-186 and rhenium-188 depends on their specific activity. Rhenium-186 is produced in low specific activity and is mainly used for labeling particles or diphosphonates for bone pain palliation. Whereas, rhenium-188 of high specific activity can be used for labeling peptides or bioactive molecules. One of the advantages of rhenium is its chemical similarity with technetium. So, diagnostic technetium analogs labeled with radiorhenium can be developed for therapeutic applications. Clinical trials promoting the use of 186/188Re-radiopharmaceuticals is, in particular, are discussed.

Radioligand therapy (RLT) as neoadjuvant treatment for inoperable pancreatic neuroendocrine tumors: a literature review.

In the last 10 years, several literature reports supported radioligand therapy (RLT) in neoadjuvant settings for pancreatic neuroendocrine tumors (PanNETs). Indeed, primary tumor shrinkage has been frequently reported following RLT in unresectable or borderline resectable PanNETs. Moreover, RLT-induced intratumoral modifications facilitate surgery, both on primary tumor and metastasis, having a great impact on progression free survival (PFS), overall survival (OS) and quality of life (QoL). However, prospective controlled investigations are necessary to confirm preliminary data and to define the best RLT scheme and the ideal patient that, in a multidisciplinary approach, should be referred to neoadjuvant RLT.

18F-Choline PET/CT or PET/MR and the evaluation of response to systemic therapy in prostate cancer: are we ready?

Purpose: During the last decade, [18F]F-choline positron emission tomography (PET) had a rising role in prostate cancer (PCa) imaging. However, despite auspicious premises, [18F]F-choline PET is not currently recommended for the evaluation of response to therapy assessment in PCa, mainly due to the lack of large-scale prospective trials. Methods: We report the cases of seven patients affected by PCa, in which [18F]F-choline PET (either with computed tomography-CT or magnetic resonance imaging-MR) contributed significantly in the systemic therapy response evaluation. Results and conclusion: [18F]F-choline PET/CT or PET/MR demonstrated to be a useful imaging modality in the assessment of response to systemic therapy in metastatic PCa patients, irrespective of the stage of disease (either in hormone sensitive and in castrate resistant condition) and the kind of systemic treatment. In most cases, PSA serum values and [18F]F-choline PET showed a synchronous disease evolution after systemic therapy. ADT can alter [18F]F-choline uptake, therefore the time of scan should be correctly planned. Finally, PET/CT with [18F]F-choline is a useful tool for reinforcing the identification of metastatic disease in case of a switch from metastatic castration sensitive to castration resistant PCa.

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives.

BACKGROUND: Renal masses detection is continually increasing worldwide, with Renal Cell Carcinoma (RCC) accounting for approximately 90% of all renal cancers and remaining one of the most aggressive urological malignancies. Despite improvements in cancer management, accurate diagnosis and treatment strategy of RCC by computed tomography (CT) and magnetic resonance imaging (MRI) are still challenging. Prostate-Specific Membrane Antigen (PSMA) is known to be highly expressed on the endothelial cells of the neovasculature of several solid tumors other than prostate cancer, including RCC. In this context, recent preliminary studies reported a promising role for positron emission tomography (PET)/CT with radiolabeled molecules targeting PSMA, in alternative to fluorodeoxyglucose (FDG) in RCC patients. PURPOSE: The aim of our review is to provide an updated overview of current evidences and major limitations regarding the use of PSMA PET/CT in RCC. METHODS: A literature search, up to 31 December 2021, was performed using the following electronic databases: PubMed, SCOPUS, Web of Science, and Google Scholar. RESULTS: The findings of this review suggest that PSMA PET/CT could represent a valid imaging option for diagnosis, staging, and therapy response evaluation in RCC, particularly in clear cell RCC. CONCLUSIONS: Further studies are needed for this "relatively" new imaging modality to consolidate its indications, timing, and practical procedures.