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

Abstract

We report findings from the first-in-human study of [¹¹C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET). Ten healthy adults were imaged according to a 90-min dynamic PET protocol after bolus intravenous injection of [¹¹C]MDTC. Five participants also completed a second [¹¹C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [¹¹C]MDTC in human brain was evaluated using tissue compartmental modeling. Four additional healthy adults completed whole-body [¹¹C]MDTC PET/CT to calculate organ doses and the whole-body effective dose. [¹¹C]MDTC brain PET and [¹¹C]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 [¹¹C]MDTC was 5.29 μSv/MBq. These data demonstrate the safety and pharmacokinetic behavior of [¹¹C]MDTC with PET in healthy human brain. Future studies identifying radiometabolites of [¹¹C]MDTC are recommended before applying [¹¹C]MDTC PET to assess the high expression of the CB2R by activated microglia in human brain.