Synthesis and Evaluation of a 18F-Labeled Triazinediamine Analogue for Imaging Mutant IDH1 Expression in Gliomas by PET.

Journal Article (Journal Article)

Mutations in the isocitrate dehydrogenase gene 1 (IDH1) are common in gliomas. Studies suggest that IDH1 mutations are early events in glioma formation and are important drivers of malignant progression. Herein, we report the synthesis and evaluation of a 18F-labeled triazinediamine analogue, [18F]1, as a candidate radiotracer for noninvasive imaging of IDH1 mutations in gliomas by positron emission tomography (PET). In vitro studies revealed good binding inhibition potency and binding affinity for [18F]1 in IDH1 mutant glioma cell lines, with a half-maximal inhibitory concentration value (IC50) of 54 nM and an equilibrium dissociation constant (Kd) of 40 nM. In vivo studies using mutant IDH1 glioma xenografts showed good tumor uptake of [18F]1 and specific inhibition by the unlabeled 1, but also elevated radioactivity uptake in the bone, suggesting significant defluorination. The results support further optimization of the triazinediamine scaffold to develop a more stable and potent 18F-labeled analogue for PET imaging of IDH1 mutations in gliomas.

Full Text

Duke Authors

Cited Authors

  • Chitneni, SK; Yan, H; Zalutsky, MR

Published Date

  • July 12, 2018

Published In

Volume / Issue

  • 9 / 7

Start / End Page

  • 606 - 611

PubMed ID

  • 30034587

Pubmed Central ID

  • PMC6047021

International Standard Serial Number (ISSN)

  • 1948-5875

Digital Object Identifier (DOI)

  • 10.1021/acsmedchemlett.7b00478


  • eng

Conference Location

  • United States