Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates

Purpose99mTc-3PRGD2 is a 99mTc-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin αvβ3 expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated 99mTc-3PRGD2 in healthy cynomolgus primates for its blood clearance kinetics, biodistribution, and radiation dosimetry.ProceduresHealthy cynomolgus primates (4.1 ± 0.7 kg, n = 5) were anesthetized, and the venous blood samples were collected via a femoral vein catheter at various time points after injection of ~555 MBq of 99mTc-3PRGD2. Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering ~555 MBq of 99mTc-3PRGD2 in the non-human primates, and the radiation dosimetry estimate was calculated.Results99mTc-3PRGD2 could be easily obtained from freeze-dried kits with high radiochemical purity (>95%) and high specific activity (~5 Ci/μmol). 99mTc-3PRGD2 had a rapid blood clearance with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min postinjection. No adverse reactions were observed up to 4 weeks after the repeated dosing. The whole-body images exhibited high kidney uptake of 99mTc-3PRGD2 and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of 99mTc-3PRGD2 were found in the kidneys (13.2 ± 1.08 μGy/MBq) and the bladder wall (33.1 ± 1.91 μGy/MBq).Conclusion99mTc-3PRGD2 can be readily available using the kit formulation. This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of 99mTc-3PRGD2 for noninvasive imaging of integrin αvβ3 in humans are warranted.