@article{4eff83cfeec54cae8b9e94aeaf6ddae1,
title = "First-in-human imaging using [11C]MDTC: a radiotracer targeting the cannabinoid receptor type 2",
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 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.",
keywords = "Cannabinoid receptor type 2, Dosimetry, Human, Pharmacokinetic, Positron emission tomography",
author = "Yong Du and Coughlin, {Jennifer M.} and Brosnan, {Mary Katherine} and Allen Chen and Shinehouse, {Laura K.} and Rehab Abdallah and Lodge, {Martin A.} and Mathews, {William B.} and Chen Liu and Yunkou Wu and Il Minn and Paige Finley and Hall, {Andrew W.} and Lesniak, {Wojciech G.} and Dannals, {Robert F.} and Horti, {Andrew G.} and Pomper, {Martin G.}",
note = "Funding Information: This publication was supported by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. We also acknowledge EB024495 for support. Funding Information: This publication was supported by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. We also acknowledge EB024495 for support. Funding Information: This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. We also acknowledge EB024495 for support. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",
year = "2023",
month = jul,
doi = "10.1007/s00259-023-06170-y",
language = "English (US)",
volume = "50",
pages = "2386--2393",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "8",
}