Immuno-PET Imaging of HER3 in a Model in which HER3 Signaling Plays a Critical Role

摘要: HER3 is overexpressed in various carcinomas including colorectal cancer (CRC), which associated with poor prognosis, and involved the development of therapy resistance. Thus, an vivo imaging technique needed to evaluate expression HER3, important therapeutic diagnostic target. Here, we report successful PET using a newly generated anti-human monoclonal antibody, Mab#58, mouse model HER3-overexpressing xenograft tumor. Furthermore, assessed role signaling CRC tissue-originated spheroid (CTOS) applied detect endogenous CTOS-derived xenografts. Cell binding assays 89Zr-labeled Mab#58 cell line HER3/RH7777 demonstrated that [89Zr]Mab#58 specifically bound cells (Kd = 2.7 nM). In biodistribution study mice bearing its parent xenografts showed tumor accumulation was significantly higher than control from day 1 4, tending increase 4 reaching 12.2 ± 4.5%ID/g. Radioactivity other tissues, xenograft, decreased or remained unchanged 6. Positron emission tomography (PET) same enabled clear visualization but not RH7777 CTOS growth assay revealed were dependent on for their growth. studies clearly visualized antibody. successfully by anti-HER3 antibody xenograft-bearing mice, retains properties patient Non-invasive targeting antibodies feasible, it expected be useful diagnosis treatment.