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(^(177)Lu)la...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(^(177)Lu)labeled monoclonal antibodies(mA bs)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 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu 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 ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21976167,U20A20384)the CAEP Innovation and Development Foundation(No.CX20200003)+2 种基金Nuclear Energy Development Project of State Administration of Science,Technology and Industry for National Defense(No.20201192–1)Key R&D Project of Sichuan Science and Technology Program(No.2020YFS0030)the Central Guidance for Local Science and Technology Development Projects(No.202138–03)。
文摘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(^(177)Lu)labeled monoclonal antibodies(mA bs)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 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu 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 ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.
