title: Distribution and pharmacokinetic analysis of angiostatin radioiodine labeled with high stability.
abstract: OBJECTIVE
  Radiotracers of anticancer agents provide important information on its in vivo handling. Angiostatin (AST) is a promising anticancer drug with potent antiangiogenic effects, but reported AST radiotracers suffer from poor in vivo stability. In this study, we synthesized an AST probe radioiodinated via the Bolton-Hunter reagent (125I-BH-AST) and investigated its stability and biokinetics in mice.
  
  
  METHODS
  125I-BH-AST and conventional direct radioiodinated 125I-AST were evaluated for human endothelial cell binding characteristics. In vivo stability of the radiotracers was compared by biodistribution studies in normal ICR mice. Angiostatin pharmacokinetics was analyzed by serial blood sampling after intravenous injection of 125I-BH-AST with varying AST concentrations in mice.
  
  
  RESULTS
  Both 125I-AST and 125I-BH-AST retained selective endothelial binding as demonstrated by dose-dependent inhibition by nonradiolabeled AST. 125I-BH-AST was substantially more stable in mice than 125I-AST, with 28- and 7-fold lower 24-h thyroid and blood activities, respectively (15.5+/-1.5 vs. 430.9+/-32.2 and 0.1+/-0.0 vs. 0.8+/-0.0 %ID/g; both P<.005). Using (125)I-BH-AST, we found that 24-h AST accumulation was highest in the kidneys, followed by the liver and lungs. Kinetic analysis of 125I-BH-AST revealed AST to have linear pharmacokinetics with a T(1/2) of 5.8+/-2.6 h, volume of distribution (V(d)) of 6.8+/-1.3 ml and clearance of 0.8+/-0.1 ml/h.
  
  
  CONCLUSIONS
  Radioiodine-labeled AST prepared by the BH method provides a radioprobe with superior stability and improved in vivo biokinetics that is useful for distribution and pharmacokinetic studies.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Song
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Paik
authors.forename: Bong-Ho
authors.initials: BH
authors.lastname: Koh
authors.forename: Joon-Sang
authors.initials: JS
authors.lastname: Bae
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Kim
mesh_terms: D043168:Angiostatins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002478:Cells, Cultured; D004355:Drug Stability; D042783:Endothelial Cells / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013388:Succinimides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D013388:Succinimides; C022581:Bolton-Hunter reagent; D043168:Angiostatins