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

Abstract

This first-inhuman study investigated the safety, biodistribution and radiation dosimetry of the novel 18 F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) positron emission tomography (PET) imaging agent, 18 F-rhPSMA-7.3. Methods: Six healthy volunteer subjects (3 males, 3 females) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 minutes after the administration of 18 F-rhPSMA-7.3 (mean activity 220; range, 210-228 MBq). PET scans were conducted in three separate sessions and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 hours post-injection to assess metabolite-corrected radioactivity in whole blood, plasma and urine. Quantitative measurements of 18 F radioactivity in volumes of interest (VOIs) over target organs were determined directly from the PET images at 8 time points and normalized time-activity concentration curves were generated. These normalized cumulated activities were then inputted into the OLINDA/EXM package to calculate the internal radiation dosimetry and the subjects' effective dose. Results: 18 F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to 18 F-rhPSMA-7.3. The calculated effective dose was 0.0141 mSv/MBq when using a 3.5-hour voiding interval. The organs with the highest absorbed dose per unit of administered radioactivity were the adrenals (mean absorbed dose, 0.1835 mSv/MBq), the kidneys (mean absorbed dose, 0.1722 mSv/MBq), the submandibular glands (mean absorbed dose, 0.1479 mSv) and the parotid glands (mean absorbed dose, 0.1137 mSv/MBq). At the end of the first scanning session (mean time, 111 min post-injection), an average of 7.2% (range, 4.4-9.0%) of the injected radioactivity of 18 F-rhPSMA-7.3 was excreted into urine. Conclusions: The safety, biodistribution and internal radiation dosimetry 18 F-rhPSMA-7.3 are considered favorable for PET imaging.

The Influence of Specific Activity on the Biodistribution of 18F-rhPSMA-7.3: A Retrospective Analysis of Clinical Positron Emission Tomography Data

“…To translate these animal data into clinical context, two different methodologies for detection of imaging-derived biodistribution of 18 F-rhPSMA-7.3 were applied. Recently, biodistribution of 18 F-rhPSMA-7.3 has been investigated in 6 healthy subjects, where 18 F-rhPSMA-7.3 showed high physiologic uptake in the kidneys and salivary glands (10). Our study demonstrated, that the uptake of most organs is not influenced by receiving lower specific activities as it might occur during clinical practice in a busy PET clinic.…”

Radiolabeled PSMA Inhibitors

“…The resulting lead candidate [ 18 F]Ga-rh-PSMA-7.3 showed the highest tumor accumulation and low uptake in non-target tissues. This was confirmed in healthy volunteers determining biodistribution and radiation dosimetry data (NCT03995888) and in a larger cohort of patients [ 84 , 195 , 196 , 197 ]. The molar activity of [ 18 F]Ga-rh-PSMA-7.3 had a minor influence on the biodistribution [ 198 , 199 ].…”

Utility of 18F-rhPSMA-7.3 PET for Imaging of Primary Prostate Cancer and Preoperative Efficacy in N-Staging of Unfavorable Intermediate- to Very High-Risk Patients Validated by Histopathology

“…In the efficacy cohort, LN metastases were present in 48/420 (11%) resected templates, in 33/166 (20%) hemi-pelvic templates and in 24/83 patients (29%). A total of 1763 nodes were removed with a median (IQR) of 20 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) per patient. A patient example is presented in Figure 3.…”

“…To date, the safety and biodistribution of 18 F-rhPSMA-7.3 have been established in healthy volunteers and PCa patients. 18 F-rhPSMA-7.3 has been shown to have low average urinary excretion and diagnostic efficacy has been demonstrated in patients with BCR of PCa (16)(17)(18). 18 F-rhPSMA-7.3 is currently under evaluation in two phase III studies, for primary and BCR PCa (NCT04186845 and NCT04186819).…”