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 ¹⁸F synthesis and utility for labeling with radiometals. Here, we assessed the biodistribution and image quality of ¹⁸F-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 ¹⁸F-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 ¹⁸F-rhPSMA-7 was similar to that of established PSMA ligands, and tumor uptake of ¹⁸F-rhPSMA-7 was stable across the administered activities and uptake times. An early imaging time point (50-70 min) is recommended for ¹⁸F-rhPSMA-7 PET/CT to achieve the highest overall image quality.

Keywords: 18F-rhPSMA-7; PET; biodistribution; prostate cancer; uptake time.

FIGURE 1.

¹⁸F-rhPSMA7 biodistribution: maximum-intensity-projection image illustrating tracer accumulation in salivary glands, liver, spleen, pancreas, bowel, kidneys, and bladder at 1 h after injection. Focal uptake (arrow) near bladder indicates lesion in prostate.

FIGURE 2.

Bar graphs displaying normal distribution according to SUV_mean (A) and SUV_mean ratio (B). These graphs display biodistribution for entire patient cohort regardless of uptake time, and error bars show 95% confidence intervals for mean (data represent all patients analyzed, including all uptake times and administered activities).

FIGURE 3.

Changes in SUV_mean ratio according to uptake time. Increase in uptake time leads to decrease in retention in blood pool but increase in accumulation in normal bone, kidneys, and urinary bladder. x-axis gives different uptake time groups (group 1, 50–70 min; group 2, 71–90 min; group 3, 91–110 min; group 4, ≥ 111 min). A, C, and D show significant trends; B (bone) has P value of 0.052.