title: Specific endothelial binding and tumor uptake of radiolabeled angiostatin.
abstract: Angiostatin (AS) is a potent antiangiogenic agent which inhibits tumor growth through specific action on proliferating endothelial cells. Imaging of radiolabeled AS would enhance our knowledge on the pharmacokinetics of AS and might provide useful information relating to tumor neovasculature. We therefore investigated the potential of radiolabeled AS as a novel tumor imaging agent. Human angiostatin was radioiodine labeled using the lactoperoxidase method. Competition binding studies showed a dose-dependent inhibition of (125)I-AS binding to endothelial cells by excess unlabeled AS, and a displacement curve demonstrated that specific binding was dose dependent and saturable, with a K(d) value of 169 n M. Gel analysis showed that (125)I-AS remained stable in serum for up to 24 h without significant degradation. Intravenously injected (125)I-AS in rats was cleared from the blood in an exponential fashion. Biodistribution data from human colon cancer-bearing Balb/C nude mice showed high uptake in the kidneys, stomach, liver, and lungs. Tumor uptake was 3.2+/-0.7, 2.6+/-0.2, and 1.7+/-0.2%ID/g at 2, 4, and 9 h after injection, respectively. Tumor to muscle count ratio increased from 3.1+/-0.5 at 2 h to 4.4+/-0.5 at 9 h. Serial scintigraphy from 1 to 5 h after (123)I-AS injection demonstrated high uptake in the kidneys and bladder, consistent with renal excretion. There was clear demarcation of tumor by 1 h, with gradual increase in contrast over time (4-h tumor to contralateral thigh ratio =4.7+/-1.1). Thus, radioiodine-labeled angiostatin binds specifically to endothelial cells and has potential as a novel tumor imaging agent.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwondong, Kangnamgu, Seoul, Korea.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Song
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Paik
authors.forename: Sang Sung
authors.initials: SS
authors.lastname: Byun
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Kim
mesh_terms: D043168:Angiostatins / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism*; D005240:Feasibility Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011485:Protein Binding; D011865:Radioisotope Dilution Technique; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D043168:Angiostatins