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

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abstract

  • 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 ╬╝Sv/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.

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

publication date

  • July 2023