title: Advantage of a residualizing iodine radiolabel for radioimmunotherapy of xenografts of human non-small-cell carcinoma of the lung.
abstract: Attachment of 131I to MAbs through adducts such as dilactitol-tyramine (DLT), which remain lysosomally trapped after catabolism of the labeled MAb, can greatly increase the residence time of the radiolabel at the tumor site. Our previous studies demonstrated a marked increase in accretion of 131I in a human lung-cancer xenograft model, using 131I-DLT in comparison to 131I linked to MAb by the conventional chloramine-T methodology.
  
  
  METHODS
  In this study, biodistribution experiments were performed to evaluate the effect of protein dose on the accretion of 131I-DLT-labeled MAb RS11 in tumor and nontumor tissues, and in vivo radioimmunotherapy experiments compared the effect of single injections of 131I-DLT-labeled MAb RS11 to conventional 131I-labeled RS11 and an untreated control group.
  
  
  RESULTS
  Dosimetry calculations based on the biodistribution data indicate only small changes in absorbed dose-to-tumor and nontumor tissues with increasing protein dose up to 100 micrograms, with a predicted absorbed dose to tumor of from 21,000 to 25,000 cGy/mCi. A single dose of 100 microCi of 131I-DLT-RS11 was found to cause tumor regression. At 7 wk postinjection of the radiolabeled MAbs, tumor volume in 73% of the animals administered 131I-DLT-labeled RS11 remained smaller than at the time of MAb injection. This is compared to 14% of the tumors in the conventionally labeled 131I-RS11 group and none in the untreated group.
  
  
  CONCLUSIONS
  The use of the residualizing radiolabel DLT provides a therapeutic advantage in comparison to conventional 131I-labeled RS11.
authors.affiliation: Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA.
authors.forename: R
authors.initials: R
authors.lastname: Stein
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: S R
authors.initials: SR
authors.lastname: Thorpe
authors.forename: M J
authors.initials: MJ
authors.lastname: Mattes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D012074:Remission Induction; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014439:Tyramine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; C049133:dilactitol tyramine; D014439:Tyramine