Biodistribution and Radiation Dosimetry of ¹²⁴I-DPA-713, a PET Radiotracer for Macrophage-Associated Inflammation.

Abstract

Whole-body PET/CT was performed using ¹²⁴I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. <b>Methods:</b> Healthy subjects aged 18-65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of ¹²⁴I-DPA-713. Time-activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the <i>TSPO</i> polymorphism rs6971, and plasma protein binding of ¹²⁴I-DPA-713 was measured. <b>Results:</b> Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4-78.1 MBq) and 469 ± 34 ng (range, 416-520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. ¹²⁴I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. <b>Conclusion:</b>¹²⁴I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.