PET imaging of [11C]MPC-6827, a microtubule-based radiotracer in non-human primate brains

Naresh Damuka; Paul W. Czoty; Ashley T. Davis; Michael A. Nader; Susan H. Nader; Suzanne Craft; Shannon L. Macauley; Lindsey K. Galbo; Phillip M. Epperly; Christopher T. Whitlow; April T. Davenport; Thomas J. Martin; James B. Daunais; Akiva Mintz; Kiran Kumar Solingapuram Sai

doi:10.3390/molecules25102289

PET imaging of [¹¹C]MPC-6827, a microtubule-based radiotracer in non-human primate brains

Naresh Damuka
, Paul W. Czoty
, Ashley T. Davis
, Michael A. Nader
, Susan H. Nader
, Suzanne Craft
, Shannon L. Macauley
, Lindsey K. Galbo
, Phillip M. Epperly
, Christopher T. Whitlow
, April T. Davenport
, Thomas J. Martin
, James B. Daunais
, Akiva Mintz
, Kiran Kumar Solingapuram Sai

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

13 Scopus citations

Abstract

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [¹¹C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [¹¹C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [¹¹C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [¹¹C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

Original language	English
Article number	2289
Journal	Molecules
Volume	25
Issue number	10
DOIs	https://doi.org/10.3390/molecules25102289
State	Published - May 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Funding

Funding: The authors acknowledge financial support for these studies provided by NIH-NIA: R01AG065839-01 (KKSS), Wake Forest Center for Research on Substance Use and Addiction (CRSUA) pilot grant (KKSS), Wake Forest Translational Alcohol Research Center P50AA026117 (Czoty), Wake Forest Center for Neurobiology of Addiction Treatment, P50DA006634-27 (Nader), NIH-NIDA: R01 DA017763 (Nader), and TIP-CTSA ULTR001420 (McClain).

Funders	Funder number
KKSS
NIA/NIH	R01AG065839-01
NIH/NIDA	R01 DA017763, TIP-CTSA ULTR001420
Wake Forest Center for Neurobiology of Addiction Treatment	P50DA006634-27
Wake Forest Translational Alcohol Research Center	P50AA026117
National Center for Advancing Translational Sciences (NCATS)	UL1TR001420

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Blood–brain barrier
Microtubule
Non-human primate
PET imaging
Reproducibility

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.3390/molecules25102289

Cite this

Damuka, N., Czoty, P. W., Davis, A. T., Nader, M. A., Nader, S. H., Craft, S., Macauley, S. L., Galbo, L. K., Epperly, P. M., Whitlow, C. T., Davenport, A. T., Martin, T. J., Daunais, J. B., Mintz, A., & Sai, K. K. S. (2020). PET imaging of [¹¹C]MPC-6827, a microtubule-based radiotracer in non-human primate brains. Molecules, 25(10), Article 2289. https://doi.org/10.3390/molecules25102289

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title = "PET imaging of [11C]MPC-6827, a microtubule-based radiotracer in non-human primate brains",

abstract = "Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer{\textquoteright}s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.",

keywords = "Blood–brain barrier, Microtubule, Non-human primate, PET imaging, Reproducibility",

author = "Naresh Damuka and Czoty, \{Paul W.\} and Davis, \{Ashley T.\} and Nader, \{Michael A.\} and Nader, \{Susan H.\} and Suzanne Craft and Macauley, \{Shannon L.\} and Galbo, \{Lindsey K.\} and Epperly, \{Phillip M.\} and Whitlow, \{Christopher T.\} and Davenport, \{April T.\} and Martin, \{Thomas J.\} and Daunais, \{James B.\} and Akiva Mintz and Sai, \{Kiran Kumar Solingapuram\}",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).",

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T1 - PET imaging of [11C]MPC-6827, a microtubule-based radiotracer in non-human primate brains

AU - Damuka, Naresh

AU - Czoty, Paul W.

AU - Davis, Ashley T.

AU - Nader, Michael A.

AU - Nader, Susan H.

AU - Craft, Suzanne

AU - Macauley, Shannon L.

AU - Galbo, Lindsey K.

AU - Epperly, Phillip M.

AU - Whitlow, Christopher T.

AU - Davenport, April T.

AU - Martin, Thomas J.

AU - Daunais, James B.

AU - Mintz, Akiva

AU - Sai, Kiran Kumar Solingapuram

N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

PY - 2020/5

Y1 - 2020/5

N2 - Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

AB - Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

KW - Blood–brain barrier

KW - Microtubule

KW - Non-human primate

KW - PET imaging

KW - Reproducibility

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