Animal biodistribution and pharmacokinetics study of ~(131)I-labelled rch24

Abstract

Objective To evaluate biodistribution and pharmacokinetics pattern of ~(131)I-labeled rch24which is the region-grafted (humanized) anti-carcinoembryonic antigen (CEA) monoclonal antibody in nude mice. Methods Nude mice bearing cancer xenografts received intravenous injections of ~(131)I- rch24, then blood, plasma, heart, liver, spleen, lung, kidney, tumor and other tissues were taken at different time point for determination the concentration of radioactivity and calculate the T/NT value. Nude mice were packeted randomly to four group of high, medium, low dose and continuous administration, blood drug concentration was detected by ELISA method at the different intervals. Then, draw the concentration-time curve and calculate the pharmacokinetics paramete. Results After administration, radioactivity of the tumour was significantly enhanced whereas radioactivity of normal tissues decreased gradually. For single administration, at the dose of low to medium, pharmacokinetics pattern was linearity -kinetics whereas for high dose group,pharmacokinetics paramete shown some behavior of non-linearity-kinetics. Conclusion Our results suggest that the ~(131)I-labeled region-grafted (humanized) anti-CEA monoclonal antibody rch24 exhibit a considerable targeting activity so as to ~(131)I radioisotopes can be concentrated specifically in tumor. The pharmacokinetics pattern of this medicine was different at different dose. Key words: Carcinoembryonic antigen; Antibodies; monoclonal; ~(131)I; Tissue distribution; Pharmacokinetics