Document Report Card

ID: ALA2203116

Journal: J Med Chem

Title: Synthesis and evaluation of novel carbon-11 labeled oxopurine analogues for positron emission tomography imaging of translocator protein (18 kDa) in peripheral organs.

Authors: Kumata K, Yui J, Hatori A, Fujinaga M, Yanamoto K, Yamasaki T, Kawamura K, Wakizaka H, Nengaki N, Yoshida Y, Ogawa M, Fukumura T, Zhang MR.

Abstract: To develop a PET ligand for imaging TSPO in peripheral organs, we designed three novel oxopurine analogues [(11)C]3a-c (LogD: 1.81-2.17) by introducing a pyridine ring in place of a benzene ring in the lead compound [(11)C]2 (LogD: 3.48). The desmethyl precursors 10 for radiosynthesis were synthesized by reacting glycine 7 with picolylamines 4, followed by hydrolysis and by Curtius rearrangement with diphenylphosphoryl azide. Methylation of 10a-c with methyl iodide produced unlabeled compounds 3a-c. The radiosynthesis of [(11)C]3a-c was performed by reacting 10a-c with [(11)C]methyl iodide. Compounds 3a-c displayed high or moderate in vitro binding affinities (K(i): 5-40 nM) for TSPO. PET with [(11)C]3a-c in rats showed high uptake in the lung, heart, and kidney, which are organs with high TSPO expression. Metabolite analysis with [(11)C]3a showed that radioactivity in these organs mainly corresponded with unchanged [(11)C]3a. PET with [(11)C]3a using a rat model of lung inflammation showed a significant signal in the lipopolysaccharide-treated lung.

CiteXplore: 21790126

DOI: 10.1021/jm200516a