First-in-human safety and biodistribution of 64Cu-25%-CANF-Comb atherosclerosis PET imaging agent
Objectives There is intense interest to develop a molecular imaging probe to detect stages of atherosclerotic plaque stability. Natriuretic peptide receptor C (NPRC) is an attractive target because it is up-regulated in various plaque components. We have developed a nanoparticle-based radiopharmaceutical,64Cu-25%-CANF-Comb, that targets this receptor and permits noninvasive plaque detection in pre-clinical models of atherosclerosis. We have now begun safety, biodistribution and dosimetry testing in human subjects.
Methods After obtaining eIND approval from the FDA for 64Cu-25%-CANF-Comb, we intravenously injected ~5.6 mCi of the radiopharmaceutical into the first 2 of 8 normal volunteers (1M, 1F; average 35 yrs). Subjects underwent a whole body PET-CT at 1-4, 5-10 and 24 hours p.i., for evaluation of biodistribution and radiation dosimetry, with vital signs (heart rate, respiratory rate, blood pressure), serum laboratory assessment, urinalysis and EKG at baseline, and p.i at imaging time points.
Results There were no significant differences in vital signs, blood or urine assays, or EKG results between baseline and post-injection values. Activity was observed to predominantly accumulate in the liver and spleen with a long blood retention time, 15% excreted through urine. Dosimetry showed the critical organ was liver at ~1 rad/mCi with an Effective Dose of 0.14 rem/mCi. Pre-clinical studies showed critical organs to be bone surface, 0.307 rad/mCi and heart, 0.245 rad/mCi.
Conclusions 64Cu-25%-CANF-Comb, a nanoparticle PET radiopharmaceutical for atherosclerosis imaging has been translated into humans. Although requiring further study, initial toxicity, biodistribution and dosimetry data suggest that this radiopharmaceutical will be safe for human use in setting the stage for more extensive studies to evaluate its diagnostic performance.