Preclinical Evaluation of 89Zr-Labeled Anti-Nectin-4 Antibody for Enhanced PET Imaging in Bladder Urothelial Carcinoma

Abstract This study evaluated the preclinical performance of a novel 89Zr-labeled anti-Nectin-4 monoclonal antibody, [89Zr]Zr-DFO-MW282, for PET imaging of bladder urothelial carcinoma (BUC). [89Zr]Zr-DFO-MW282 was prepared via p-isothiocyanatobenzyl-desferrioxamine (p-NCS-Bn-DFO) conjugation, achieving a radiolabeling yield exceeding 70%, radiochemical purity ≥95% post-purification, and specific activity of 36.10−63.72 GBq/μmol. [89Zr]Zr-DFO-MW282 selectively accumulated in Nectin-4-positive cells and tumors, with uptake blocked by the unlabeled MW282 antibody. Small-animal PET/CT imaging revealed sustained tumor uptake in SW780 xenografts, with a high SUVmean value of 4.46 ± 0.02 at 120 h p.i. Owing to hepatobiliary clearance, the kidney and bladder uptake was minimal, yielding excellent imaging contrast. The probe demonstrated high specificity, prolonged tumor retention, and negligible bladder background, making it a promising immuno-PET probe for precise imaging of BUC and warranting further clinical translation.