Phase I Clinical Study with the GRPR-Antagonist [^99mTc]Tc-DB8 for SPECT Imaging of Prostate Cancer: Does the Injected...

Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [^99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [^99mTc]Tc-DB8 peptide (n = 5-6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [^99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUV_max 1.65-9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [^99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40-120 µg. An injected peptide mass of 80-120 µg/patient and SPECT acquisition 2-4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys.