A Novel 99m Tc-Labeled Quinazoline-Based Isocyanide Probe for EGFR Imaging: Synthesis and Biological Evaluation

The epidermal growth factor receptor (EGFR) is a critical therapeutic target that is overexpressed in various solid tumors; however, existing EGFR tyrosine kinase inhibitors (EGFR-TKIs) are limited by efficacy and the development of resistance. To enable noninvasive visualization of EGFR expression for patient stratification, this study developed a novel 99m Tc-labeled quinazoline derivative, [ 99m Tc][Tc-(CN-PEG 2 -QZL) 6 ] +, as a potential single-photon emission computed tomography (SPECT) imaging agent. The probe was conveniently prepared via a lyophilized kit formulation with high radiochemical purity and demonstrated good stability in vitro . Cellular studies in EGFR-overexpressing A431 cells demonstrated efficient cellular uptake and internalization, which was partially suppressible by EGFR-TKIs. Biodistribution studies in A431 tumor-bearing mice revealed tumor accumulation, with significantly reduced uptake upon preadministration of a competing EGFR inhibitor, validating target specificity. SPECT/CT imaging further corroborated the ability of the probe to visualize EGFR-overexpressing tumors, with observable signal reduction in blocking studies. Despite persistent liver uptake, a common challenge for this class of agents, [ 99m Tc][Tc-(CN-PEG 2 -QZL) 6 ] +, represents a readily prepared proof-of-concept SPECT tracer for targeting EGFR-overexpressing malignancies that warrants further structural optimization to improve its pharmacokinetic profile.