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

• Published in: Journal of Nuclear Medicine Vol. 59; no. 11; pp. 1751 - 1756
• Main Authors: Foss, Catherine A, Plyku, Donika, Ordonez, Alvaro A, Sanchez-Bautista, Julian, Rosenthal, Hailey B, Minn, Il, Lodge, Martin A, Pomper, Martin G, Sgouros, George, Jain, Sanjay K
• Format: Journal Article
• Language: English
• Published: United States 01.11.2018
• Subjects: Acetamides - administration & dosage; Acetamides - pharmacokinetics; Adult; Female; Genotype; Healthy Volunteers; Humans; Inflammation - diagnostic imaging; Inflammation - immunology; Inflammation - metabolism; Iodine Radioisotopes - administration & dosage; Iodine Radioisotopes - pharmacokinetics; Macrophages - immunology; Macrophages - metabolism; Male; Middle Aged; Polymorphism, Single Nucleotide; Positron Emission Tomography Computed Tomography - methods; Pyrazoles - administration & dosage; Pyrazoles - pharmacokinetics; Pyrimidines - administration & dosage; Pyrimidines - pharmacokinetics; Radiation Dosage; Radioligand Assay; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - pharmacokinetics; Receptors, GABA - genetics; Receptors, GABA - metabolism; Tissue Distribution; Whole Body Imaging - methods; Young Adult; macrophage; sarcoidosis; DPA-713; PET/CT; pyrazolopyrimidine
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.117.207431

Whole-body PET/CT was performed using I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. 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 I-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 polymorphism rs6971, and plasma protein binding of I-DPA-713 was measured. 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. I-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. I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.