Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb 188Re-HAb18

Abstract

AIM:To label anti-hepatoma monoclonal antibody (mAb) fragment HAb18 F(ab')2 was labeled with 188Re for the pharmacokinetic model of 188Re-HAb18 F(ab')2 and to evaluate its pharmacokinetic parameters in hepatoma-bearing nude mice. METHODS:HAb18 F(ab')2 was directly labeled with 188Re using 2-mercaptoethanol (2-ME) as reducing agents. Labeling efficiency and immunoreactivity of 188Re-HAb18 F(ab')2 were evaluated by Whatman 3MM paper chromatography and live cell assay, respectively. Biodistribution analysis was also conducted in nude mice bearing human hepatoma in which animals were sacrificed at different time points (1, 4, 18, 24 and 24h) after 188Re-HAb18 F(ab')2 was injected through tail-vein into hepatoma-bearing nude mice. The blood and radioactivity of organs and mass were measured. The concentrations of (188)Re-HAb18 F(ab')2 were evaluated with a pharmacokinetic 3P97 software. RESULTS:The optimum labeling efficiency and immunoreactive fraction were 91.7% and 0.78% respectively. The parameters of 188Re-HAb18 F(ab')2 were: T (1/2),2.29 h;Vd,1.49 x 10(-9)L x Bq(-1);AUC, 20.49 x 10(9)Bq x h x L(-1);CL, 0.45 x 10(-3)L x h(-1). 188Re-HAb18 F(ab')2 could locate specially in hepatoma with high selective reactivity of HAb18 F(ab')2. 188Re-HAb18 F(ab')2 was mainly eliminated by kidney. The maximal tumor to blood ratio was at 48 h,and maximal tumor to liver ratio was at 18 h. CONCLUSION:The pharmacokinetics of 188Re-HAb18 F(ab')2 fit a l-compartment model. 188Re-HAb18 F(ab')2 can be uptaken selectively at the hepatoma site.