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

Yong Du; Jennifer M. Coughlin; 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

doi:10.1007/s00259-023-06170-y

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

Yong Du, Jennifer M. Coughlin, 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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 (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 [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.

Original language	English (US)
Pages (from-to)	2386-2393
Number of pages	8
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	50
Issue number	8
DOIs	https://doi.org/10.1007/s00259-023-06170-y
State	Published - Jul 2023

Keywords

Cannabinoid receptor type 2
Dosimetry
Human
Pharmacokinetic
Positron emission tomography

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Access to Document

10.1007/s00259-023-06170-y

Cite this

Du, Y., Coughlin, J. M., Brosnan, M. K., Chen, A., Shinehouse, L. K., Abdallah, R., Lodge, M. A., Mathews, W. B., Liu, C., Wu, Y., Minn, I., Finley, P., Hall, A. W., Lesniak, W. G., Dannals, R. F., Horti, A. G., & Pomper, M. G. (2023). First-in-human imaging using [¹¹C]MDTC: a radiotracer targeting the cannabinoid receptor type 2. European Journal of Nuclear Medicine and Molecular Imaging, 50(8), 2386-2393. https://doi.org/10.1007/s00259-023-06170-y

Du, Y , Coughlin, JM, Brosnan, MK, Chen, A, Shinehouse, LK, Abdallah, R, Lodge, MA , Mathews, WB, Liu, C, Wu, Y, Minn, I, Finley, P, Hall, AW, Lesniak, WG , Dannals, RF , Horti, AG & Pomper, MG 2023, 'First-in-human imaging using [¹¹C]MDTC: a radiotracer targeting the cannabinoid receptor type 2', European Journal of Nuclear Medicine and Molecular Imaging, vol. 50, no. 8, pp. 2386-2393. https://doi.org/10.1007/s00259-023-06170-y

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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 = "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",

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T1 - First-in-human imaging using [11C]MDTC

T2 - a radiotracer targeting the cannabinoid receptor type 2

AU - Du, Yong

AU - Coughlin, Jennifer M.

AU - Brosnan, Mary Katherine

AU - Chen, Allen

AU - Shinehouse, Laura K.

AU - Abdallah, Rehab

AU - Lodge, Martin A.

AU - Mathews, William B.

AU - Liu, Chen

AU - Wu, Yunkou

AU - Minn, Il

AU - Finley, Paige

AU - Hall, Andrew W.

AU - Lesniak, Wojciech G.

AU - Dannals, Robert F.

AU - Horti, Andrew G.

AU - Pomper, Martin G.

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Cannabinoid receptor type 2

KW - Dosimetry

KW - Human

KW - Pharmacokinetic

KW - Positron emission tomography

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