.188 Re Labeled Human Hepatoma Monoclonal Antibody Fragment Hab18 F (ab ') 2 In Liver Cancer-bearing Nude Mice In Vivo Pharmacokinetics And 188re-beta-ray Induced Apoptosis Of Hepatoma Cells

HAb18 is a high affinity monocloonal antibody against hepatocellular carcinima membrane protein. Previous study proved that HAb18 has a fine tumor localization in tumor xenograft nude mice and HCC patients. 188Re is a new nuclide, its half-life is 17hours. 188Re has been applied in the research of tumor. In this work, 188Re-labeied hepatoma McAb fragment HAb18 F(ab ' )2 was injected to the nude mice for the research of pharmacokinetics of this radioimmunoconjugates,and apoptosis in HCC cell line induced by188Re-β irradiation was also discussed.1.Study on the pharmacokinetics of radioimmunotherapeutic agent HAb18 F (ab ' ) 2 in hepatoma-bearing nude miceThe monoclonal antibody fragments HAb18 F(ab ' )2 were labeled with l88Re using high efficience iodination method. The radioimmunoconjugates were intravenously administered to mude mice. The mouse whole-body and blood radioactivity cpm were mearsured in different time point. Redistribution was ivestigated by killing mouse in different time point and anatomy it,then measured majority organs' weight and radioactivity cpm respectively. The main results were as follows:(1)The pharmacokinetics of 188Re-HAb18 F(ab ' )2 fitted a 1-compartment model.The clearance rate was relevant to injection doses,and the higer injected dose produced low clearance values.(2) 188Re-HAb18 F(ab' )2 could locate specially in hepatoma withhigh elective reactivity of HAblS F(ab' )2.The level of radiation in tumor sustained highly for a long time while other organs' clearance was fast. l88Re-HAbl 8 F(ab' )2 was mainly eliminated by kidney.(3) The parameters of 188Re-HAbl8 F(ab' )2 were Tl/2 2.29h, Vdl.49xKr9L.Bq', AUC 20.49x lO'Bq.h.I/1, CL 0.45 x l(T3L.h'1.2. l88Re-P ray induced apoptosis of HCCApoptosis in HCC cell line induced by internal exposure from radionuclide 188Re was qualitatively and quantitatively studied with specific mrthods. There were apoptosis bodies in the fluorescence scope. Under electric microscope the HCC' s microvillus were gone and chromation concentrated to the edge of nuclear. Flow Cytometry demonstrated Gl sub-peak of apoptosis cells.A typical DNA ladder pattern appeared on agarose gel electrophoresis.