Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations. Among the most utilized radiotracers, [⁶⁸Ga]- and [¹⁸F]-labeled PSMA tracers enable precise imaging even with low disease burden. This diagnostic precision also supports advanced therapeutic approaches, including metastasis-directed therapy for oligometastatic cases and systemic treatment options, such as radioligand therapy, which presents new treatment perspectives for metastatic, castration-resistant PCa. This review examines the evolution of PSMA-PET in the diagnostics and therapy of PCa while comparing the current recommendations from leading clinical guidelines. The integration of PSMA-PET into clinical practice has redefined the management of PCa, improving diagnostic accuracy and enabling personalized treatment strategies, while lacking prospective long-term outcome data. As PSMA-PET continues to expand in clinical application, this review highlights its significant advancements while critically addressing limitations to ensure balanced and evidence-based implementation in prostate cancer care.

Background: Liver uptake in [⁶⁸Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [⁶⁸Ga]Ga-PSMA-11 was replaced by [¹⁸F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]F-PSMA-1007. Methods: Fifty patients who underwent PET examinations in two centers with both [¹⁸F]F-PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUV_mean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison. Results: Liver SUV_mean was significantly higher with [¹⁸F]F-PSMA-1007 (11.7 ± 3.9) compared to [⁶⁸Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUV_mean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUV_mean on [¹⁸F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUV_mean [⁶⁸Ga]Ga-PSMA-11 = 0.33 x SUV_mean [¹⁸F]F-PSMA-1007 + 1.52 (r = .78, p < .001). Conclusion: Comparing biodistribution of [⁶⁸Ga]Ga and [¹⁸F]F tracers, liver uptake on [⁶⁸Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [¹⁸F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [¹⁸F]F-PSMA-1007 as a basis for RLT selection.

Background: Investigation of the clinical feasibility of dynamic whole-body (WB) [¹⁸F]FDG PET, including standardized uptake value (SUV), rate of irreversible uptake (Ki), and apparent distribution volume (Vd) in physiologic tissues, and comparison between inflammatory/infectious and cancer lesions. Methods: Twenty-four patients were prospectively included to undergo dynamic WB [¹⁸F]FDG PET/CT for clinically indicated re-/staging of oncological diseases. Parametric maps of Ki and Vd were generated using Patlak analysis alongside SUV images. Maximum parameter values (SUV_max, Ki_max, and Vd_max) were measured in liver parenchyma and in malignant or inflammatory/infectious lesions. Lesion-to-background ratios (LBRs) were calculated by dividing the measurements by their respective mean in the liver tissue. Results: Seventy-seven clinical target lesions were identified, 60 malignant and 17 inflammatory/infectious. Ki_max was significantly higher in cancer than in inflammatory/infections lesions (3.0 vs. 2.0, p = 0.002) while LBRs of SUV_max, Ki_max, and Vd_max did not differ significantly between the etiologies: LBR (SUV_max) 3.3 vs. 2.9, p = 0.06; LBR (Ki_max) 5.0 vs. 4.4, p = 0.05, LBR (Vd_max) 1.1 vs. 1.0, p = 0.18). LBR of inflammatory/infectious and cancer lesions was higher in Ki_max than in SUV_max (4.5 vs. 3.2, p < 0.001). LBRs of Ki_max and SUV_max showed a strong correlation (Spearman’s rho = 0.83, p < 0.001). Conclusions: Dynamic WB [¹⁸F]FDG PET/CT is feasible in a clinical setting. LBRs of Ki_max were higher than SUV_max. Ki_max was higher in malignant than in inflammatory/infectious lesions but demonstrated a large overlap between the etiologies.

Objectives: The objective of this study was to assess the feasibility and accuracy of a fully automated artificial intelligence (AI) powered coronary artery calcium scoring (CACS) method on ungated CT in oncologic patients undergoing 18F-FDG PET/CT. Methods: A total of 100 oncologic patients examined between 2007 and 2015 were retrospectively included. All patients underwent 18F-FDG PET/CT and cardiac SPECT myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin within 6 months. CACS was manually performed on non-contrast ECG-gated CT scans obtained from SPECT-MPI (i.e., reference standard). Additionally, CACS was performed using a cloud-based, user-independent tool (AI-CACS) on ungated CT scans from 18F-FDG-PET/CT examinations. Agatston scores from the manual CACS and AI-CACS were compared. Results: On a per-patient basis, the AI-CACS tool achieved a sensitivity and specificity of 85% and 90% for the detection of CAC. Interscore agreement of CACS between manual CACS and AI-CACS was 0.88 (95% CI: 0.827, 0.918). Interclass agreement of risk categories was 0.8 in weighted Kappa analysis, with a reclassification rate of 44% and an underestimation of one risk category by AI-CACS in 39% of cases. On a per-vessel basis, interscore agreement of CAC scores ranged from 0.716 for the circumflex artery to 0.863 for the left anterior descending artery. Conclusions: Fully automated AI-CACS as performed on non-contrast free-breathing, ungated CT scans from 18F-FDG-PET/CT examinations is feasible and provides an acceptable to good estimation of CAC burden. CAC load on ungated CT is, however, generally underestimated by AI-CACS, which should be taken into account when interpreting imaging findings.

Purpose: Hypophysitis occurs in up to 10% of patients treated with immune-checkpoint inhibitors (ICIs). MRI shows no abnormalities of the pituitary gland in one third of patients. A delayed diagnosis increases the risk for life-threatening adrenal crisis, underscoring the need for early detection. This study evaluates the diagnostic accuracy FDG PET/CT in detecting ICI-induced hypophysitis in a cohort of melanoma patients. Materials and Methods: Patients with metastatic melanoma and ICI-induced hypophysitis, who underwent FDG PET/CT 90 days before to 10 days after diagnosis, were compared with an age- and sex-matched control group of patients undergoing ICI treatment without signs of hypophysitis. The ratio of SUV_max of the pituitary gland to the SUV_mean of the blood pool (target-to-background ratio [TBR]) was calculated. Diagnostic accuracy of the TBR was assessed using area under the receiver operating characteristics curve analysis. Results: A total of 28 patients was included. The majority of patients with hypophysitis received ipilimumab/nivolumab (64.3%, 9/14). Visual assessment of the TBR distribution demonstrated a positive correlation with decreasing time to diagnosis. To evaluate diagnostic performance, only patients with FDG PET/CT 50 days before to 8 days after diagnosis (11/14) were included. TBR was significantly higher in these compared with the control group (median [interquartile range], 2.78 [2.41] vs 1.59 [0.70], respectively; P = 0.034). A sensitivity of 72.7% and a specificity of 90.9% were achieved at a TBR threshold of 2.41 (area under the receiver operating characteristics curve = 0.769). Conclusions: Our findings suggest that, in patients undergoing ICI treatment for metastatic melanoma, a pituitary TBR of approximately 2.4 may indicate impending ICI-induced hypophysitis.