title: Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb 188Re-HAb18.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell Engineering Research Centre, Fourth Military Medical University, Xi'an 710033, Shaanxi Province, China. wall1970@sina.com
authors.forename: Chao
authors.initials: C
authors.lastname: Lou
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Bian
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Shou-Bo
authors.initials: SB
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy*; D007140:Immunoglobulin Fab Fragments; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes; D012211:Rhenium; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D011868:Radioisotopes; D012211:Rhenium