title: Biodistribution of 211At-labeled humanized monoclonal antibody A33.
abstract: Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.
authors.affiliation: Unit of Radiology, Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Sweden, and Department of Clinical Physiology and Nuclear Medicine, PET and Cyclotron Unit, Rigshospitalet, Copenhagen, Denmark. Ylva.Almqvist@radiol.uu.se
authors.forename: Ylva
authors.initials: Y
authors.lastname: Almqvist
authors.forename: Ann-Charlott
authors.initials: AC
authors.lastname: Steffen
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics*; D001246:Astatine; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays