Quantitative and Qualitative Analyses of Biodistribution and PET Image Quality of a Novel Radiohybrid PSMA, ¹⁸F-rhPSMA-7, in Patients with Prostate Cancer

Abstract

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.

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

“…Furthermore, the novel tracer outperformed morphologic imaging for N-staging of high-risk primary prostate cancer, with efficacy comparable to the literature data for [ 68 Ga]Ga-PSMA-11 [17]. The highest imaging quality of this tracer was obtained at 50-70 min post injection in PET/CT [18].…”

“…Due to the superior nuclear properties of the fluorine-18 radionuclide and accompanying logistic and economic advantages [10,11], a shift of interest from 68 Ga-labeled PSMA tracers toward 18 F-labeled analogues has been observed in recent years [12][13][14]. In this context radiohybrid (rh) PSMA ligands, developed by our group, form a novel class of radiopharmaceuticals, which combine a Silicon-Fluoride-Acceptor (SiFA) and a metal chelate (or a chelator) in a single molecule [15].…”

“…Such rhPSMA ligands can either be labeled with fluorine-18 by isotopic exchange at the SiFA-moiety in the presence of a non-radioactive metal chelate (e.g., nat Ga-or nat Luchelate), or with a radiometal (e.g., [ 68 Ga]Gallium, [ 177 Lu] Lutetium, [ 225 Ac]Actinium) by means of the chelator, while the SiFA moiety is non-radioactive [15]. The chemical identity of the 18 7) has already been assessed for PET imaging of primary and metastatic castration-resistant prostate cancer. Biodistribution of [ 18 F, nat Ga]rhPSMA-7 was found to be similar to that of established PSMA ligands, and [ 18 F, nat Ga]rhPSMA-7 PET/CT demonstrated high detection rates in early biochemical recurrence after radical prostatectomy, especially among patients with low prostate-specific antigen values [16].…”

Safety, Biodistribution, and Radiation Dosimetry of 18F-rhPSMA-7.3 in Healthy Adult Volunteers

“…To fully determine the potential of a new PET tracer, assessing the extent of physiological uptake in normal organs is essential in order to establish its usefulness for detecting disease in these organs. In general, the biodistribution of 18 F-rhPSMA-7.3 was found to be similar to that of other PSMA-based tracers, typically showing high uptake in salivary glands and the kidneys, and in line with the known expression of PSMA in these healthy tissues (1,35). Whilst possible binding to PSMA present in the kidneys may not negatively affect prostate imaging, it may interfere with the detection of primary tumors of the kidney.…”

A rare case of polyostotic fibrous dysplasia detected on 18F-rhPSMA-7 PET/CT

“…In addition, it is increasingly being used as an imaging modality for initial staging [3]. 18 F-rhPSMA-7 is a new theranostic PSMA-targeting agent which allows radiolabeling with 18 F and radiometals and is associated with minimal renal excretion [4]. However, physiologic and other pathologic forms of tracer uptake have to be considered carefully as potential pitfalls to image interpretation, such as ganglia, healing fracture, adrenal adenoma, primary lung cancer, and metastatic renal cell carcinoma [5].…”