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

Abstract

This first-in-humans study investigated the safety, biodistribution, and radiation dosimetry of a novel ¹⁸F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) PET imaging agent, ¹⁸F-rhPSMA-7.3. Methods: Six healthy volunteers (3 men, 3 women) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 min after the administration of ¹⁸F-rhPSMA-7.3 (mean activity, 220; range, 210-228 MBq). PET scans were conducted in 3 separate sessions, and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 h after injection to assess metabolite-corrected radioactivity in whole blood, plasma, and urine. Quantitative measurements of ¹⁸F radioactivity in volumes of interest 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:¹⁸F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to ¹⁸F-rhPSMA-7.3. The calculated effective dose was 0.0141 mSv/MBq when using a 3.5-h voiding interval. The organs with the highest mean absorbed dose per unit of administered radioactivity were the adrenals (0.1835 mSv/MBq), the kidneys (0.1722 mSv/MBq), the submandibular glands (0.1479 mSv), and the parotid glands (0.1137 mSv/MBq). At the end of the first scanning session (mean time, 111 min after injection), an average of 7.2% (range, 4.4%-9.0%) of the injected radioactivity of ¹⁸F-rhPSMA-7.3 was excreted into urine. Conclusion: The safety, biodistribution, and internal radiation dosimetry of ¹⁸F-rhPSMA-7.3 are considered favorable for PET imaging.

Keywords: 18F; PSMA; biodistribution; dosimetry; rhPSMA.

FIGURE 1.

¹⁸F-rhPSMA-7.3 PET schedule. Scans and their total duration are represented as black boxes, and breaks are represented as gray boxes. All scans were conducted from vertex to mid thigh, apart from scan 5 (26 min), which was conducted from vertex to feet.

FIGURE 2.

PET images of representative healthy volunteer after administration of ¹⁸F-rhPSMA-7.3. First scan session was at 1–90 min after injection, second was at 150–178 min, and third was at 220–248 min. Subject was permitted to leave PET scanner and void urine between sessions.

FIGURE 3.

Radioactivity concentration of ¹⁸F-rhPSMA-7.3 in whole blood as function of time. x-axis values represent mean time of sample collection, and y-axis values represent mean activity, from all subjects.

FIGURE 4.

Organ-specific relative uptake (top 6 organs).