18 F-labeled prostate-specific membrane antigen (PSMA)-ligand PET has several principal advantages over 68 Ga-PSMA-11. The purpose of this retrospective study was to evaluate the frequency of non-tumor-related uptake and the detection efficacy comparing 68 Ga-PSMA-11 PET/CT and 18 F-PSMA-1007 PET/CT in recurrent prostate cancer (PC) patients. Methods: The study included 102 patients with biochemically recurrent PC after radical prostatectomy undergoing 18 F-PSMA-1007 PET/CT imaging. On the basis of various clinical variables, patients with corresponding 68 Ga-PSMA-11 PET/CT scans were matched. All PET/CT scans (n 5 204) were reviewed by 1 nuclear medicine physician. First, all PET-positive lesions were noted. Then, lesions suspected of being recurrent PC were differentiated from lesions attributed to a benign origin on the basis of known pitfalls and information from CT. For each region, the SUV max of the lesion with the highest PSMA-ligand uptake was noted. Detection rates were determined, and SUV max was compared separately for 68 Ga-PSMA-11 and 18 F-PSMA-1007. Results: In total, 18 F-PSMA-1007 PET and 68 Ga-PSMA-11 PET revealed 369 and 178 PSMA-ligand-positive lesions, respectively. 18 F-PSMA-1007 PET revealed approximately 5 times more lesions attributed to a benign origin than did 68 Ga-PSMA-11 PET (245 vs. 52 lesions, respectively). The benign lesions most frequently observed were ganglia, unspecific lymph node, and bone lesions, at a rate of 43%, 31%, and 24% for 18 F-PSMA-1007 PET and 29%, 42%, and 27% for 68 Ga-PSMA-11 PET, respectively. The SUV max of lesions attributed to a benign origin was significantly higher (P , 0.0001) for 18 F-PSMA-1007 PET. Further, a similar number of lesions was attributed to recurrent PC (124/369 for 18 F-PSMA-1007 PET and 126/178 for 68 Ga-PSMA-11 PET). Conclusion: The number of lesions with increased PSMA-ligand uptake attributed to a benign origin is considerably higher for 18 F-PSMA-1007 PET than for 68 Ga-PSMA-11 PET. This finding indicates the need for sophisticated reader training emphasizing known pitfalls and reporting within the clinical context.

Our preliminary results suggest that Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance ofGa-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of Ga-PSMA PET as an imaging biomarker for response assessment.

Our aim was to introduce and validate qPSMA, a semiautomatic software package for whole-body tumor burden assessment in prostate cancer patients using 68 Ga-prostate-specific membrane antigen (PSMA) 11 PET/CT. Methods: qPSMA reads hybrid PET/ CT images in DICOM format. Its pipeline was written using Python and C11 languages. A bone mask based on CT and a normaluptake mask including organs with physiologic 68 Ga-PSMA11 uptake are automatically computed. An SUV threshold of 3 and a liver-based threshold are used to segment bone and soft-tissue lesions, respectively. Manual corrections can be applied using different tools. Multiple output parameters are computed, that is, PSMA ligand-positive tumor volume (PSMA-TV), PSMA ligand-positive total lesion (PSMA-TL), PSMA SUV mean , and PSMA SUV max . Twenty 68 Ga-PSMA11 PET/CT data sets were used to validate and evaluate the performance characteristics of qPSMA. Four analyses were performed: validation of the semiautomatic algorithm for liver background activity determination, assessment of intra-and interobserver variability, validation of data from qPSMA by comparison with Syngo.via, and assessment of computational time and comparison of PSMA PET-derived parameters with serum prostate-specific antigen. Results: Automatic liver background calculation resulted in a mean relative difference of 0.74% (intraclass correlation coefficient [ICC], 0.996; 95%CI, 0.989;0.998) compared with METAVOL. Intraand interobserver variability analyses showed high agreement (all ICCs . 0.990). Quantitative output parameters were compared for 68 lesions. Paired t testing showed no significant differences between the values obtained with the 2 software packages. The ICC estimates obtained for PSMA-TV, PSMA-TL, SUV mean , and SUV max were 1.000 (95%CI, 1.000;1.000), 1.000 (95%CI, 1.000;1.000), 0.995 (95%CI, 0.992;0.997), and 0.999 (95%CI, 0.999;1.000), respectively. The first and second reads for intraobserver variability resulted in mean computational times of 13.63 min (range, 8.22-25.45 min) and 9.27 min (range, 8.10-12.15 min), respectively (P 5 0.001). Highly significant correlations were found between serum prostate-specific antigen value and both PSMA-TV (r 5 0.72, P , 0.001) and PSMA-TL (r 5 0.66, P 5 0.002). Conclusion: Semiautomatic analyses of whole-body tumor burden in 68 Ga-PSMA11 PET/CT is feasible. qPSMA is a robust software package that can help physicians quantify tumor load in heavily metastasized prostate cancer patients.

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The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)] ( 68 Ga-PSMA ligand; PSMA is prostate-specific membrane antigen) PET/CT in patients with biochemical recurrent prostate cancer defined by Phoenix criteria after external-beam radiotherapy or brachytherapy as primary treatment. Methods: One hundred eighteen patients with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range, 2.2-158.4 ng/mL; interquartile range, 4.2-10.2 ng/mL) were finally eligible for this retrospective analysis. Seventy-seven and 41 patients had been treated by external-beam radiotherapy or brachytherapy, respectively. Of the 118 patients, 45 were receiving androgen-deprivation therapy (ADT) within at least 6 mo before the PET/CT. The detection rates were stratified by PSA. The influence of primary Gleason score and ADT was assessed. Relationships between SUV and clinical as well as pathologic features in patients with positive findings were analyzed using univariate and multivariable linear regression models. Results: One hundred seven of 118 patients (90.7%) showed pathologic findings indicative for tumor recurrence in 68 Ga-PSMA ligand PET/CT. The detection rates were 81.8% (36/44), 95.3% (41/43), and 96.8% (30/31) for PSA of 2 to ,5, 5 to ,10, and $10 ng/mL, respectively (P 5 0.0377). 68 Ga-PSMA ligand PET/CT indicated local recurrence in 68 of 107 patients (63.5%), distant lesions in 64 of 107 patients (59.8%), and local recurrence as well as distant lesions in 25 of 107 patients (23.4%). The detection rate was significantly higher in patients with ADT (97.7%) versus without ADT (86.3%, P 5 0.0381), but independent from primary Gleason score $ 8 (92.0%) versus # 7 (90.2%, P 5 0.6346). SUV max and SUV mean were significantly associated with PSA and ADT (P 5 0.018 and 0.004 for SUV max , respectively; P 5 0.025 and 0.007 for SUV mean , respectively). Conclusion: 68 Ga-PSMA ligand PET/CT demonstrates high detection rates in patients with biochemical recurrence of prostate cancer after primary radiation therapy. The detection rate was positively associated to increasing PSA as well as concomitant ADT. 68 Ga-PSMA ligand PET/CT enables discrimination of local versus metastatic disease and thus might have a crucial impact on further clinical management. A major limitation of this study is the lack of histopathologic proof in most patients.

Radiohybrid PSMA (rhPSMA) ligands, a new class of theranostic prostate-specific membrane antigen (PSMA)-targeting agents, feature fast 18 F synthesis and utility for labeling with radiometals. Here, we assessed the biodistribution and image quality of 18 F-rhPSMA-7 to determine the best imaging time point for patients with prostate cancer. Methods: In total, 202 prostate cancer patients who underwent a clinically indicated 18 F-rhPSMA-7 PET/CT were retrospectively analyzed, and 12 groups based on the administered activity and uptake time of PET scanning were created: 3 administered activities (low, 222-296 MBq; moderate, 297-370 MBq; and high, 371-444 MBq) and 4 uptake time points (short, 50-70 min; intermediate, 71-90 min; long, 91-110 min; and extra long, $111 min). For quantitative analyses, SUV mean and organ-or tumor-to-background ratio were determined for background, healthy organs, and 3 representative tumor lesions. Qualitative analyses assessed overall image quality, nonspecific blood-pool activity, and background uptake in bone or marrow using 3-or 4-point scales. Results: In quantitative analyses, SUV mean showed a significant decrease in the blood pool and lungs and an increase in the kidneys, bladder, and bones as the uptake time increased. SUV mean showed a trend to increase in the blood pool and bones as the administered activity increased. However, no significant differences were found in 377 tumor lesions with respect to the administered activity or uptake time. In qualitative analyses, the overall image quality was stable along with the uptake time, but the proportion rated to have good image quality decreased as the administered activity increased. All other qualitative image parameters showed no significant differences for the administered activities, but they showed significant trends with increasing uptake time: less nonspecific blood activity, more frequent background uptake in the bone marrow, and increased negative impact on clinical decision making. Conclusion: The biodistribution of 18 F-rhPSMA-7 was similar to that of established PSMA ligands, and tumor uptake of 18 F-rhPSMA-7 was stable across the administered activities and uptake times. An early imaging time point (50-70 min) is recommended for 18 F-rhPSMA-7 PET/CT to achieve the highest overall image quality.

PET combined with CT and prostate-specific membrane antigen (PSMA) ligands has gained significant interest for staging prostate cancer (PC). In this study, we propose 2 multimodal quantitative indices as imaging biomarkers for the assessment of osseous tumor burden using Ga-PSMA PET/CT and present preliminary clinical data. We defined 2 bone PET indices (BPIs) that incorporate anatomic information from CT and functional information from Ga-PSMA PET: BPI is the percentage of bone volume affected by tumor and BPI additionally considers the level of PSMA expression. We describe a semiautomatic computation method based on segmentation of bones in CT and of lesions in PET. Data from 45 patients with castration-resistant PC and bone metastases during Ra-dichloride were retrospectively analyzed. We evaluated the computational stability and reproducibility of the proposed indices and explored their relation to the prostate-specific antigen blood value, the bone scan index (BSI), and disease classification using PERCIST. On the technical side, BPI and BPI showed an interobserver maximum difference of 3.5%, and their computation took only a few minutes. On the clinical side, BPI and BPI showed significant correlations with BSI ( = 0.76 and 0.74, respectively, < 0.001) and prostate-specific antigen values ( = 0.57 and 0.54, respectively, < 0.01). When the proposed indices were compared against expert rating using PERCIST, BPI and BPI showed better agreement than BSI, indicating their potential for objective response evaluation. We propose the evaluation of BPI and BPI as imaging biomarkers for Ga-PSMA PET/CT in a prospective study exploring their potential for outcome prediction in patients with bone metastases from PC.

Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using nearinfrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics. Our aim was to investigate whether clinical multispectral optoacoustic tomography (MSOT) could enable the label-free imaging of muscle perfusion and oxygenation under clinically relevant challenges: the arterial and venous occlusion. We employed a hybrid clinical MSOT/ultrasound system equipped with a hand-held scanning probe to visualize hemodynamic and oxygenation changes in skeletal muscle under arterial and venous occlusions. Four (N = 4) healthy volunteers were scanned over the forearm for both 3-minute occlusion challenges. MSOT-recorded pathophysiologically expected results during tests of disturbed blood flow with high resolution and without the need for contrast agents. During arterial occlusion, MSOT-extracted Hb-values showed an increase, while HbO 2 -and total blood volume (TBV)-values remained roughly steady, followed by a discrete increase during the hyperemic period after cuff deflation. During venous occlusion, results showed a clear increase in intramuscular HbO 2 , Hb and TBV within the segmented muscle area. MSOT was Angelos Karlas and Michael Kallmayer contributed equally to the study.