Screening for a 177Lu-labeled CA19–9 monoclonal antibody via PET imaging for colorectal cancer therapy

Carbohydrate antigen 19–9 (CA19–9) with multi epitopes relatively high expresses on colorectal cancer (CRC) cells, making it an attractive target for developing radioimmunotherapy (RIT) for CRC. The lutetium-177 (177Lu) labeled monoclonal antibodies (mAbs) can selectively bind the corresponding antigens and release targeted cytotoxic radiation, which could induce cell apoptosis and reduce the drug-induced resistance. Here, a series of CA19–9 mAbs were labeled with zirconium-89 (89Zr), and one with high tumor uptake was screened via PET imaging, which has potential application for the diagnosis of CRC. Then the screened mAb (C003) labeled with 177Lu was utilized for CA19–9 targeted RIT, which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone. Meanwhile, the side effects of 177Lu-DOTA-C003 are limited according to the results of in vivo study. Both 89Zr-DFO-C003 for CRC immune-PET imaging and 177Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications. A 177Lu-labeled CA19–9 monoclonal antibody was screened via PET imaging for colorectal cancer therapy. [Display omitted]