First-in-human imaging using [ 11 C]MDTC: a radiotracer targeting the cannabinoid receptor type 2

Purpose We report findings from the first-in-human study of [ 11 C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET). Methods Ten healthy adults were imaged according to a 90-min dynamic PET protocol after bolus intravenous injection of [ 11 C]MDTC. Five participants also completed a second [ 11 C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [ 11 C]MDTC in human brain was evaluated using tissue compartmental modeling. Four additional healthy adults completed whole-body [ 11 C]MDTC PET/CT to calculate organ doses and the whole-body effective dose. Results [ 11 C]MDTC brain PET and [ 11 C]MDTC whole-body PET/CT was well-tolerated. A murine study found evidence of brain-penetrant radiometabolites. The model of choice for fitting the time activity curves (TACs) across brain regions of interest was a three-tissue compartment model that includes a separate input function and compartment for the brain-penetrant metabolites. Regional distribution volume ( V T ) values were low, indicating low CB2R expression in the brain. Test-retest reliability of V T demonstrated a mean absolute variability of 9.91%. The measured effective dose of [ 11 C]MDTC was 5.29 μSv/MBq. Conclusion These data demonstrate the safety and pharmacokinetic behavior of [ 11 C]MDTC with PET in healthy human brain. Future studies identifying radiometabolites of [ 11 C]MDTC are recommended before applying [ 11 C]MDTC PET to assess the high expression of the CB2R by activated microglia in human brain.