First-in-human imaging using [C-11]MDTC: a radiotracer targeting the cannabinoid receptor type 2
European journal of nuclear medicine and molecular imaging(2023)
Abstract
PurposeWe report findings from the first-in-human study of [C-11]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET).MethodsTen healthy adults were imaged according to a 90-min dynamic PET protocol after bolus intravenous injection of [C-11]MDTC. Five participants also completed a second [C-11]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [C-11]MDTC in human brain was evaluated using tissue compartmental modeling. Four additional healthy adults completed whole-body [C-11]MDTC PET/CT to calculate organ doses and the whole-body effective dose.Results[C-11]MDTC brain PET and [C-11]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 [C-11]MDTC was 5.29 mu Sv/MBq.ConclusionThese data demonstrate the safety and pharmacokinetic behavior of [C-11]MDTC with PET in healthy human brain. Future studies identifying radiometabolites of [C-11]MDTC are recommended before applying [C-11]MDTC PET to assess the high expression of the CB2R by activated microglia in human brain.
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Key words
Cannabinoid receptor type 2,Positron emission tomography,Human,Pharmacokinetic,Dosimetry
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