Comparison of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-peptide-ChL6, a novel immunoconjugate with catabolizable linker, to 2-iminothiolane-2-[p-(bromoacetamido)benzyl]-DOTA-ChL6 in breast cancer xenografts.

摘要: Radioimmunotherapy using 131I-ChL6 antibody has shown promise in patients with breast cancer. To enhance this potential, a novel ChL6 immunoconjugate that is catabolizable and tightly binds 90Y (111)In was developed. The immunoconjugate, 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-peptide-ChL6, consists of the macrocyclic chelator DOTA linked to by peptide preferentially catabolized liver. pharmacokinetic dosimetric properties radioimmunoconjugates (RICs) (111)In- 90Y-DOTA-peptide-ChL6 90Y-2-iminothiolane (2-IT)-2-[p-(bromoacetamido)benzyl]-DOTA-ChL6 were compared athymic mice bearing HBT3477 human cancer xenografts. Each RICs stable vivo concentrated well Liver concentration, cumulative radioactivity (activity over time), radiation dose DOTA-peptide-ChL6 one-third one-half those corresponding 2-IT-2-[p(bromoacetamido)benzyl]-DOTA-ChL6 RICs. Indium-111 imperfect tracers for RICs, although their pharmacokinetics dosimetries similar. results study consistent previously published vitro data, which indicated linker cathepsin B. activities doses liver 2-IT linker. Preliminary data from pilot studies are accord these observations. These DOTA-peptide seem have excellent clinical potential radioimmunotherapy associated marrow transplantation, likely be limiting 90Y.