Identifying nonsmall-cell lung tumours bearing the T790M EGFR TKI resistance mutation using PET imaging

Area of Science:

• Oncology
• Radiochemistry
• Pharmacology

Background:

• Specific mutations in epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) significantly impact lung cancer treatment response.
• Identifying patients with resistance mutations like T790M is a critical clinical challenge for effective therapy selection.

Purpose of the Study:

• To evaluate the in vitro efficacy and in vivo performance of a novel radiotracer, [18F]FEWZ.
• To assess the biodistribution and binding specificity of [18F]FEWZ to tumors with wild-type, L858R, and T790M EGFR mutations.

Main Methods:

• In vitro assessment of [18F]FEWZ efficacy compared to its parent compound.
• In vivo biodistribution studies in tumor-bearing models.
• Evaluation of specific binding to EGFR wild-type, L858R, and T790M mutated tumors.

Main Results:

• [18F]FEWZ demonstrated efficacy in vitro.
• In vivo studies confirmed biodistribution and specific binding to target EGFR mutations.
• [18F]FEWZ successfully targeted T790M mutation-bearing tumors.

Conclusions:

• [18F]FEWZ is the first radiolabeled third-generation anilinopyrimidine-derived tyrosine kinase inhibitor.
• This tracer shows potential for in vivo imaging of T790M mutation-bearing lung tumors.
• It offers a new tool for identifying patients who may benefit from targeted therapies.