title: Biodistribution and localization of radiolabeled NR-LU-10 Fab fragment in human breast cancer xenografts.
abstract: Radioimmunodetection, which takes advantage of tumor-specific or tumor-associated radio-labeled monoclonal antibodies or other biologic molecules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The difficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohistochemical and in vivo evaluation of tumor localization and biodistribution of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab recognizes a pancarcinoma glycoprotein antigen found on tumors of epithelial cell origin. NR-LU-10 Fab reacted with 6/6 (100%) breast cancer cell lines and 14/16 (87.5%) breast tumors with varying degrees of immunostaining intensities. Athymic mice bearing ZR-75-1 breast cancer xenografts were injected with 125I-labeled NR-LU-10 Fab (12 microg/5 microCi) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58+/-1.59% of injected dose/gram [% ID/g] of tissue); this gradually decreased to 0.13+/-0.05% ID/g of tissue by 72 h postinjection of the radiolabeled Fab. Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), followed by rapid clearance over the 72-h test period. NR-LU-10 Fab displays adequate breast tumor localization with minimal biolocalization to normal tissues, thus supporting its potential use in radioimmunoscintigraphy and the RIGS system (radioimmunoguided surgery).
authors.affiliation: Department of Surgery, College of Medicine, The Ohio State University, and The Arthur G. James Cancer Hospital and Research Institute, Columbus 43210, USA. burak.1@osu.edu
authors.forename: W E
authors.initials: WE
authors.lastname: Burak
authors.forename: L
authors.initials: L
authors.lastname: DePalatis
authors.forename: R
authors.initials: R
authors.lastname: Nines
authors.forename: C
authors.initials: C
authors.lastname: Hitchcock
authors.forename: G
authors.initials: G
authors.lastname: Hinkle
authors.forename: D
authors.initials: D
authors.lastname: Houchens
authors.forename: W B
authors.initials: WB
authors.lastname: Farrar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D008223:Lymphoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments