title: Preclinical evaluation of 67Cu-labeled intact and fragmented anti-colon carcinoma monoclonal antibody MAb35.
abstract: The anti-carcinoembryonic antigen murine monoclonal antibody MAb35 and its F(ab')2 fragment were labeled with 131I or the potential therapeutic nuclide 67Cu. In vivo distribution patterns were compared in nude mice bearing human tumor xenografts by coinjection of the 131I- and 67Cu-labeled materials, thereby minimizing variations due to xenograft and host animal. The results showed that the 67Cu-labeled intact MAb35 achieved twice the percentage of injected dose/g tumor when compared to its 131I-labeled counterpart, without significant impairment of the wholebody distribution pattern. However, this effect was not evident in the case of F(ab')2, where high uptake of 67Cu was found in the kidney without any enhancement of accumulation in the target xenografts. To investigate the underlying causes of the different distribution patterns observed, iodine labeling was also performed using a more stable linkage, and the results indicated that the observed differences cannot be explained by simple deiodination of conventionally labeled preparations. We conclude that the intact form of the 67Cu-labeled antibody may be superior to the F(ab')2 fragment for use in our intended clinical studies. Our continuing work on the processing of radiometal-labeled F(ab')2 fragments, at the systemic and cellular level, will hopefully lead to a strategy to circumvent the problem of high kidney accumulation.
authors.affiliation: Paul Scherrer Institute, Wuerenlingen, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Alberto
authors.forename: P
authors.initials: P
authors.lastname: Blaeuenstein
authors.forename: I
authors.initials: I
authors.lastname: Novak-Hofer
authors.forename: H R
authors.initials: HR
authors.lastname: Maecke
authors.forename: P A
authors.initials: PA
authors.lastname: Schubiger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000276:immunology* / Q000532:radiotherapy; D003301:Copper Radioisotopes / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes