Design and 99mTc-radiolabeling of an imidazopyridine-hydrazone hybrid: A promising tumor-targeted radiopharmaceutical.

Abstract

A novel imidazopyridine-hydrazone Schiff base ligand, N'-(2-hydroxybenzylidene)-2-(1H-imidazo[1,2-a]pyridin-3-yl)acetohydrazide (HIPAH), was synthesized, characterized, and evaluated as a potential tumor-imaging radiopharmaceutical. The ligand exhibited moderate antiproliferative activity against MCF-7, HepG2, and A549 cancer cell lines with IC50 values of 18.6 ± 1.2, 24.3 ± 1.5, and 32.8 ± 2.1 μM, respectively. Radiolabeling with technetium-99m was successfully achieved with a maximum radiochemical yield of 98.2 ± 0.6% under optimized conditions. The resulting 99mTc-HIPAH complex demonstrated excellent in vitro stability, retaining 96.8 ± 0.6% and 94.5 ± 0.9% radiochemical purity after 24 h in saline and serum, respectively. Molecular docking suggested a favorable interaction of the 99mTc-HIPAH complex within the VEGFR2 binding site, with a predicted binding affinity of -9.3 kcal/mol. Biodistribution studies in Ehrlich solid tumor-bearing mice showed progressive tumor uptake reaching 7.92 ± 0.33 %ID/g at 4 h post-injection, accompanied by rapid blood clearance and a maximum tumor-to-non-target ratio of 8.61. These findings support further investigation of 99mTc-HIPAH as a potential candidate for tumor imaging by SPECT.

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