title: Anti-CEA monoclonal antibody: technetium-99m labeling and the validation process of a scintigraphic animal model with a non-cellular antigenic implant.
abstract: Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations. The utilization of labelled anti-tumor monoclonal antibodies (MoAb) in experimental models often requires implant of human antigens (usually a cellular implant), which cannot be achieved in immunocompetent animals. Our purpose was to label an anti-CEA MoAb with technetium-99m (99Tc) and to validate a simplified animal model using a noncellular antigenic implant. MoAb was directly labelled with 99mTc, after reduction with 2-mercaptoethanol. Labeling efficiency was checked by ascending chromatography and immunoreactive fraction was measured in plastic wells sensitized with the antigen. Radiopharmaceutical biodistribution was evaluated by dissection and scintigraphy in 5 mice groups; following the subcutaneous administration of Al(OH)3, CEA adsorbed Al(OH)2 and a control group evaluation. Labeling efficiency was 94+/-3%, which showed to be stable for 24 hr, with immunoreactive fraction above 50%. Invasive biodistribution evaluation showed prolonged blood retention, hepatic and renal uptake. A significant increase in uptake was observed in scintigraphic studies of animals with CEA-adsorbed Al(OH)3 implants compared with the other groups (p<0.05). The non-cellular antigenic implant model simplifies the pre-clinical evaluation of labelled MoAb.
authors.affiliation: Department of Radiology, São Paulo University Medical School, Cerqueira César, Brazil. mtsapienza@hotmail.com
authors.forename: Marcelo Tatit
authors.initials: MT
authors.lastname: Sapienza
authors.forename: Fabio Luiz Navarro
authors.initials: FL
authors.lastname: Marques
authors.forename: Miriam Roseli Yoshie
authors.initials: MR
authors.lastname: Okamoto
authors.forename: Fausto Haruki
authors.initials: FH
authors.lastname: Hironaka
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Buchpiguel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D023421:Models, Animal; D009928:Organ Specificity; D011877:Radionuclide Imaging; D013667:Technetium / Q000008:administration & dosage; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D018796:Immunoconjugates; D013667:Technetium