Synthesis and evaluation of [99mTc]Tc–octapa–necitumumab for targeted imaging of squamous non-small cell lung cancer

Abstract

This study reports the synthesis and in vitro as well as in vivo evaluation of [^99mTc]Tc–octapa–necitumumab for targeted imaging of squamous non-small cell lung cancer (NSCLC). Necitumumab was conjugated with p-SCN-Bn–H₄Octapa and efficiently labeled with technetium-99m under mild conditions, yielding excellent radiochemical purity and favorable in vitro stability. The [^99mTc]Tc–octapa–necitumumab presented strong EGFR-specific in vitro binding and internalization in HCC827 cells. Biodistribution studies in tumor-bearing mice showed a tumor uptake of 5.85 ± 0.1% ID/g at 4 h post-injection, with promising tumor-to-organ ratios, including 2.07 ± 0.18 for tumor-to-blood, 2.49 ± 0.20 for tumor-to-blocked tumor, 2.21 ± 0.18 for tumor-to-liver, 2.02 ± 0.15 for tumor-to-lung, 1.14 ± 0.06 for tumor-to-kidney, and 3.44 ± 0.57 for tumor-to-muscle. Rabbit SPECT studies validated selective tumor localization with insignificant off-target accumulation. These findings categorize [^99mTc]Tc–octapa–necitumumab as a novel radiotracer with potential for EGFR-targeted imaging in squamous NSCLC.