Targeting VEGF With ^99mTc‐Labeled Ranibizumab for Noninvasive Diagnosis of Non‐Small Cell Lung Cancer

Angiogenesis, particularly driven by the overexpression of vascular endothelial growth factor (VEGF), plays a crucial role in the growth and metastasis of tumors, making VEGF a significant target in the diagnosis and therapy of non-small cell lung cancer (NSCLC). In this work, the potential of ^99mTc-labeled ranibizumab was investigated for the non-invasive diagnosis of NSCLC. To that end, ranibizumab (RNB), a VEGF-neutralizing antibody, was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza1,4,7,10-tetra(2-carbamoylmethyl) cyclododecane (TCMC) followed by labeling with technetium-99m (^99mTc) using different reaction parameters. The ^99mTc-TCMC-RNB was characterized in terms of the percent radiochemical purity (% RCP) up to 6 h, in vitro stability in serum up to 16 h, internalization kinetics in A549 cells, and biodistribution using the NSCLC Sprague Dawley rat model. The ^99mTc-labeled TCMC-RNB exhibited 98.3 ± 0.2% RCP in normal saline, stability in rat serum with an overall decay of 32.10% within 18 h, and specific binding to A549 NSCLC cells. Biodistribution studies showed significant tumor uptake. These findings suggest that ^99mTc-labeled TCMC-RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF-related malignancies, particularly in NSCLC.