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 (Lu-177) 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 (Zr-89), 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 Lu-177 was utilized for CA19-9 targeted RIT, which presents a significant suppression effect on the growth of co1o205 xenografts than immunotherapy alone. Meanwhile, the side effects of Lu-177-DOTA-0003 are limited according to the results of in vivo study. Both Zr-89-DFO-0003 for CRC immune-PET imaging and 177 Lu-DOTA-0003 for RIT against CRC exhibit good potential in clinical applications. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.