Improved Synthesis of [11C]COU and [11C]PHXY, Evaluation of Neurotoxicity, and Imaging of MAOs in Rodent Heart

Allen F Brooks; Anthony J Mufarreh; Xia Shao; Tanpreet Kaur; Jenelle Stauff; Janna Arteaga; Michael R Kilbourn; Peter J H Scott

doi:10.1021/acsmedchemlett.0c00419

Improved Synthesis of [¹¹C]COU and [¹¹C]PHXY, Evaluation of Neurotoxicity, and Imaging of MAOs in Rodent Heart

ACS Med Chem Lett. 2020 Aug 28;11(11):2300-2304. doi: 10.1021/acsmedchemlett.0c00419. eCollection 2020 Nov 12.

Authors

Allen F Brooks¹, Anthony J Mufarreh¹, Xia Shao¹, Tanpreet Kaur¹, Jenelle Stauff¹, Janna Arteaga¹, Michael R Kilbourn¹, Peter J H Scott^{1

2

3}

Affiliations

¹ Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States.
² Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States.
³ Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

Abstract

The radiotracers [¹¹C]COU and [¹¹C]PHXY are potential PET imaging agents for in vivo studies of monoamine oxidases (MAOs), as previously shown in rodent and primate brain. One-pot, automated methods for the radiosynthesis of [¹¹C]PHXY and [¹¹C]COU were developed to provide reliable and improved radiochemical yields. Although derived from the structure of the neurotoxin MPTP, COU did not exhibit in vivo neurotoxicity to dopaminergic nerve terminals in the mouse brain as assayed by losses of VMAT2 radioligand binding. PET imaging studies in rats demonstrated that both [¹¹C]COU and [¹¹C]PHXY exhibit retention in cardiac tissues that can be blocked by pretreatment with the MAO inhibitors deprenyl (MAO-B) and pargyline (MAO-A and -B). In addition to prior neuroimaging applications, [¹¹C]COU and [¹¹C]PHXY are thus also of interest for studies of MAO enzymatic activity and imaging of sympathetic nerve density in heart.