Synthesis and evaluation in monkey of [18F]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 18F]FIMX): A promising radioligand for PET imaging of brain metabotropic glutamate receptor 1 (mGluR1)

Rong Xu, Paolo Zanotti-Fregonara, Sami S. Zoghbi, Robert L. Gladding, Alicia E. Woock, Robert B. Innis, Victor W. Pike

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

We sought to develop a PET radioligand that would be useful for imaging human brain metabotropic subtype 1 receptors (mGluR1) in neuropsychiatric disorders and in drug development. 4-Fluoro-N-methyl-N-(4-(6-(methylamino) pyrimidin-4-yl)thiazol-2-yl)benzamide (FIMX, 11) was identified as having favorable properties for development as a PET radioligand. We developed a method for preparing [18F]11 in useful radiochemical yield and in high specific activity from [18F]fluoride ion and an N-Boc-protected (phenyl)aryliodonium salt precursor (15). In baseline experiments in rhesus monkey, [18F]11 gave high brain radioactivity uptake, reflecting the expected distribution of mGluR1 with notably high uptake in cerebellum, which became 47% lower by 120 min after radioligand injection. Pharmacological challenges demonstrated that a very high proportion of the radioactivity in monkey brain was bound specifically and reversibly to mGluR1. [18F]11 is concluded to be an effective PET radioligand for imaging mGluR1 in monkey brain and therefore merits further evaluation in human subjects.

Original languageEnglish (US)
Pages (from-to)9146-9155
Number of pages10
JournalJournal of Medicinal Chemistry
Volume56
Issue number22
DOIs
StatePublished - Nov 27 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Synthesis and evaluation in monkey of [<sup>18</sup>F]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ <sup>18</sup>F]FIMX): A promising radioligand for PET imaging of brain metabotropic glutamate receptor 1 (mGluR1)'. Together they form a unique fingerprint.

Cite this