First-in-human imaging using [11C]MDTC: a radiotracer targeting the cannabinoid receptor type 2
- Resource Type
- Original Paper
- Authors
- Du, Yong; Coughlin, Jennifer M.; Brosnan, Mary Katherine; Chen, Allen; Shinehouse, Laura K.; Abdallah, Rehab; Lodge, Martin A.; Mathews, William B.; Liu, Chen; Wu, Yunkou; Minn, Il; Finley, Paige; Hall, Andrew W.; Lesniak, Wojciech G.; Dannals, Robert F.; Horti, Andrew G.; Pomper, Martin G.
- Source
- European Journal of Nuclear Medicine and Molecular Imaging. :1-8
- Subject
- Cannabinoid receptor type 2
Positron emission tomography
Human
Pharmacokinetic
Dosimetry
- Language
- English
- ISSN
- 1619-7070
1619-7089
Purpose: 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).Methods: 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.Results: [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 (VT) values were low, indicating low CB2R expression in the brain. Test-retest reliability of VT demonstrated a mean absolute variability of 9.91%. The measured effective dose of [11C]MDTC was 5.29 μSv/MBq.Conclusion: 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.