Novel ImmunoPET Probes [ 64 Cu]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 ([ 64 Cu]Cu-NOTA-GGB02-F9) based on the SEZ6-targeting antibody, GGB02-F9, for use in preclinical mouse models of SCLC. The diagnostic potential of [ 64 Cu]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 < 0.01) at 24, 48, and 72 h postinjection. The uptake of the tumor tracer in mice was found to be associated with SEZ6 expression, as determined by immunohistochemical analysis. Our study demonstrated that [ 64 Cu]Cu-NOTA-GGB02-F9 can noninvasively evaluate SEZ6 expression in preclinical SCLC mouse models.