Novel ImmunoPET Probes [64Cu]Cu-NOTA-GGB02-F9 for Small-Cell Lung Cancer Derived from a SEZ6-Targeting Antibody

Seizure-related 6 homologue (SEZ6) is a highly expressed transmembrane protein that has emerged as a promising therapeutic target for small-cell lung cancer (SCLC). In this study, we developed a novel immuno-positron emission tomography probe ([64Cu]Cu-NOTA-GGB02-F9) based on the SEZ6-targeting antibody, GGB02-F9, for use in preclinical mouse models of SCLC. The diagnostic potential of [64Cu]Cu-NOTA-GGB02-F9 was evaluated in preclinical SCLC models with varying levels of SEZ6 expression. The H69 tumors exhibited a distinct accumulation of tracer uptake in the tumor xenograft mice, reaching a maximum uptake at 72 h postinjection, which was significantly higher than that in the H69 GGB02-F9-blocked and H460 groups (P 64Cu]Cu-NOTA-GGB02-F9 can noninvasively evaluate SEZ6 expression in preclinical SCLC mouse models.