H. Manning
Faculty Member
Last active: 3/22/2018

Evaluation of the novel TSPO radiotracer 2-(7-butyl-2-(4-(2-([F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide in a preclinical model of neuroinflammation.

Tang D, Fujinaga M, Hatori A, Zhang Y, Yamasaki T, Xie L, Mori W, Kumata K, Liu J, Manning HC, Huang G, Zhang MR
Eur J Med Chem. 2018 150: 1-8

PMID: 29505933 · DOI:10.1016/j.ejmech.2018.02.076

Translocator Protein (18 kDa, TSPO) is regarded as a useful biomarker for neuroinflammation imaging. TSPO PET imaging could be used to understand the role of neuroinflammation in brain diseases and as a tool for evaluating novel therapeutic effects. As a promising TSPO probe, [F]DPA-714 is highly specific and offers reliable quantification of TSPO in vivo. In this study, we further radiosynthesized and evaluated another novel TSPO probe, 2-(7-butyl-2-(4-(2-[F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([F]VUIIS1018A), which features a 700-fold higher binding affinity for TSPO than that of [F]DPA-714. We evaluated the performance of [F]VUIIS1018A using dynamic in vivo PET imaging, radiometabolite analysis, in vitro autoradiography assays, biodistribution analysis, and blocking assays. In vivo study using this probe demonstrated high signal-to-noise ratio, binding potential (BP), and binding specificity in preclinical neuroinflammation studies. Taken together, these findings indicate that [F]VUIIS1018A may serve as a novel TSPO PET probe for neuroinflammation imaging.

Copyright © 2018. Published by Elsevier Masson SAS.

MeSH Terms (21)

Animals Disease Models, Animal Dose-Response Relationship, Drug Fluorine Radioisotopes Humans Inflammation Ischemia Male Mice Molecular Probes Molecular Structure Positron-Emission Tomography Pyrazoles Pyrimidines Radioactive Tracers Radiopharmaceuticals Rats Rats, Sprague-Dawley Receptors, GABA Structure-Activity Relationship Tissue Distribution

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