Purpose: Improved logistics and availability led to a rapid increase in the use of [¹⁸F]-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to [⁶⁸ Ga]-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in [¹⁸F]-PSMA-1007 PET. Methods: We retrospectively analyzed [¹⁸F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUV_max < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUV_max), localized, and correlated to clinical parameters, such as age, PSA, injected dose, Gleason score, tumor size (T1–T4), and type of PET scanner (analog vs. digital). Additionally, clinical and imaging follow-up results and therapeutic impact were evaluated. Results: UBUs were identified in 179 out of 348 patients (51.4%). The most frequent localizations were ribs (57.5%) and pelvis (24.8%). The frequency of UBUs was not associated with PSA, Gleason score, tumor size, age, or the injected [¹⁸F]-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital PET/CT scans (n = 74, 82%) than analog PET/CT scans (n = 221, 40.3%) (p = .0001) but not in digital PET/MR (n = 53, 51%) (p = .1599). In 80 out of 179 patients (44.7%), the interpretation of UBUs was critical for therapeutic management and therefore considered clinically relevant. For 65 UBUs, follow-ups were available: three biopsies, three radiotherapies with PSA follow-up, and 59 cases with imaging. After follow-up, UBUs were still considered unclear in 28 of 65 patients (43%), benign in 28 (43%), and malignant in nine (14%) patients. Conclusion: UBUs occur in two-thirds of patients imaged with [¹⁸F]-PSMA-1007 PET/CT and are significantly more frequent on digital PET scanners than analog scanners. UBUs should be interpreted carefully to avoid over-staging.

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.

Purpose: Recently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [⁶⁸Ga]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm²/1000 s) values in comparison to [⁶⁸Ga]PSMA uptake on PET/MRI. Methods: We retrospectively evaluated patients who underwent [⁶⁸Ga]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUV_max for PSMA uptake and ADC_mean for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson’s test for categorical correlation, Cohen’s kappa test for interrater agreement, and ROC curve to determine the best cutoff. Results: Sixty-two patients were included (mean PSA 11.7 ± 12.5). The interrater agreement between both pathologists was almost perfect with κ = 0.81. While 25 lesions had an EXP-growth with an ADC_mean of 0.777 ± 0.109, 37 showed an INF-growth with a significantly higher ADC_mean of 1.079 ± 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUV_max for the EXP-growth (19.2 ± 10.9) versus the INF-growth (9.4 ± 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADC_mean could be observed (p = 0.982 and p = 0.861, respectively). Conclusion: PCa with INF-growth showed significantly lower SUV_max and higher ADC_mean values compared to PCa with EXP-growth. Within the growth groups, ADC_mean values were independent from ISUP grading.

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.

Objectives: To evaluate the impact of fully automatic motion correction by data-driven respiratory gating (DDG) on positron emission tomography (PET) image quality, lesion detection and patient management. Materials and Methods: A total of 149 patients undergoing PET/CT for cancer (re-)staging were retrospectively included. Patients underwent a PET/CT on a digital detector scanner and for every patient a PET data set where DDG was enabled (PETDDG) and as well as where DDG was not enabled (PETnonDDG) was reconstructed. All PET data sets were evaluated by two readers which rated the general image quality, motion effects and organ contours. Further, both readers reviewed all scans on a case-by-case basis and evaluated the impact of PETDDG on additional apparent lesion, change of report, and change of management. Results: In 85% (n = 126) of the patients, at least one bed position was acquired using DDG, resulting in mean scan time increase of 4:37 min per patient in the whole study cohort (n = 149). General image quality was not rated differently for PETnonDDG and PETDDG images (p = 1.000) while motion effects (i.e. indicating general blurring) was rated significantly lower in PETDDG images and organ contours, including liver and spleen, were rated significantly sharper using PETDDG as compared to PETnonDDG (all p < 0.001). In 27% of patients, PETDDG resulted in a change of the report and in a total of 12 cases (8%), PETDDG resulted in a change of further clinical management. Conclusion: Deviceless DDG provided reliable fully automatic motion correction in clinical routine and increased lesion detectability and changed management in a considerable number of patients. Advances in knowledge: DDG enables PET/CT with respiratory gating to be used routinely in clinical practice without external gating equipment needed.

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.