title: Biodistribution and dosimetry of In-111/Y-90-HuCC49ΔCh2 (IDEC-159) in patients with metastatic colorectal adenocarcinoma.
abstract: BACKGROUND
  CC49, an antibody (mAb) reactive to tumor-associated glycoprotein (TAG-72), has been extensively studied for radioimmunotherapy for colon cancer. Myelotoxicity has been dose-limiting because of prolonged circulation time in the plasma, and human anti-mouse antibody responses were observed in the majority of patients. A CH2 domain deleted and humanized CC49 (HuCC49ΔCh2) was developed to ameliorate these problems. This study reports biodistribution and dosimetry of (111)In/(90)Y-HuCC49ΔCh2 (IDEC-159).
  
  
  METHODS
  Five (5) patients with colon cancer were enrolled. Each patient received intravenous administration of 185 MBq (111)In-HuCC49ΔCh2, followed by sequential gamma camera imaging, and blood counting. Uptakes and clearance half-lives for organs and tumors were quantified from images. Absorbed doses for (90)Y-HuCC49ΔCh2 were derived from (111)In-HuCC49ΔCh2 kinetic data.
  
  
  RESULTS
  Compared to reported (111)In/(90)Y-CC49 data in the literature, median blood circulation T(1/2β) was less at 38 (31-43) hours for (90)Y-HuCC49ΔCh2, than 50 hours for (90)Y-CC49. Median tumor-to-marrow absorbed dose ratio was 18 for (90)Y-HuCC49ΔCh2, and 9.53 for (90)Y-CC49. Median tumor-to-liver absorbed dose ratio was 3.14 for (90)Y-HuCC49ΔCh2, and 1.0 for (90)Y-CC49. Median tumor-to-spleen absorbed dose was 3.19 for (90)Y-HuCC49ΔCh2, and 1.07 for (90)Y-CC49.
  
  
  CONCLUSIONS
  A humanized and CH2 domain-deleted CC49 antibody radiolabeled with (111)In/(90)Y showed improved tumor-to-normal dose ratios over those reported from studies with intact CC49.
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. sshen@uabmc.edu
authors.forename: Sui
authors.initials: S
authors.lastname: Shen
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.forename: Ruby F
authors.initials: RF
authors.lastname: Meredith
authors.forename: Albert F
authors.initials: AF
authors.lastname: LoBuglio
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D016499:Radioimmunotherapy / Q000379:methods; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging / Q000379:methods; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; C091202:B72.3 antibody; D000922:Immunotoxins; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes