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 journalArticlepeer-review

9 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 languageEnglish
Article number2289
JournalMolecules
Volume25
Issue number10
DOIs
StatePublished - 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/).

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

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