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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Data availability

The datasets generated and analyzed in this study are available from the corresponding author on reasonable request.

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Acknowledgements

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

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.

Author information

Authors and Affiliations

  1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 601 N. Caroline St., JHOC 3223, Baltimore, MD, 21287, USA

    Yong Du, Mary Katherine Brosnan, Allen Chen, Laura K. Shinehouse, Rehab Abdallah, Martin A. Lodge, William B. Mathews, Chen Liu, Yunkou Wu, Il Minn, Paige Finley, Andrew W. Hall, Wojciech G. Lesniak, Robert F. Dannals, Andrew G. Horti & Martin G. Pomper

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, 21287, USA

    Jennifer M. Coughlin & Martin G. Pomper

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  1. Yong Du
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  11. Il Minn
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Contributions

YD, JC, ML, AH, and MP contributed to the study conception and design. Material preparation, data collection, and analysis were performed by all authors. The first draft of the manuscript was written by YD and JC, and each author read, edited, and approved the final manuscript.

Corresponding author

Correspondence to Martin G. Pomper.

Ethics declarations

Ethics approval

This study was approved by the Johns Hopkins Institutional Review Board and was conducted under a FDA-approved US investigational new drug application (IND 131367). All experimental animal protocols were performed in accordance with relevant federal and state laws and institutional guidelines and approved by the Animal Care and Use Committee of the Johns Hopkins Medical Institutions.

Consent to participate

Written, informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

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Du, Y., Coughlin, J.M., Brosnan, M.K. et al. First-in-human imaging using [11C]MDTC: a radiotracer targeting the cannabinoid receptor type 2. Eur J Nucl Med Mol Imaging 50, 2386–2393 (2023). https://doi.org/10.1007/s00259-023-06170-y

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  • DOI: https://doi.org/10.1007/s00259-023-06170-y

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