Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent.

ABSTRACT:

Purpose

Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first ¹⁸F-labelled ATM inhibitor [¹⁸F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics.

Methods

Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [¹⁸F]fluoride. Uptake of [¹⁸F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with s

SUBMITTER: Fraser CR 

PROVIDER: S-EPMC9375819 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature