Safety, biodistribution and radiation dosimetry of 18 F-rhPSMA-7.3 in healthy adult volunteers

Abstract

This first-in-human study investigated the safety, biodistribution and radiation dosimetry of the novel ¹⁸F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) positron emission tomography (PET) imaging agent, ¹⁸F-rhPSMA-7.3. <b>Methods:</b> 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 ¹⁸F-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 ¹⁸F 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. <b>Results:</b> ¹⁸F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to ¹⁸F-rhPSMA-7.3: because of the temporal association with ¹⁸F-rhPSMA-7.3 injection, a causal relationship could not be excluded. 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 ¹⁸F-rhPSMA-7.3 was excreted into urine. <b>Conclusion:</b> The safety, biodistribution and internal radiation dosimetry ¹⁸F-rhPSMA-7.3 are considered favorable for PET imaging.