Synthesis and preclinical evaluation of [¹¹C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor.

ABSTRACT:

Background

Mutations in the epidermal growth factor receptor (EGFR) kinase domain are common in non-small cell lung cancer. Conventional tyrosine kinase inhibitors target the mutation site in the ATP binding pocket, thereby inhibiting the receptor's function. However, subsequent treatment resistance mutations in the ATP binding site are common. The EGFR allosteric inhibitor, EAI045, is proposed to have an alternative mechanism of action, disrupting receptor signaling independent of the ATP-binding site. The antibody cetuximab is hypothesized to increase the number of accessible allosteric pockets for EAI045, thus increasing the potency of the inhibitor. This work aimed to gain further knowledge on pharmacokinetics, the EGFR mutation-targeting potential, and the influence of cetuxim

SUBMITTER: Hognasbacka AA 

PROVIDER: S-EPMC10873260 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature