title: The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.
abstract: The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.
authors.affiliation: Department of Pathology, Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: E V
authors.initials: EV
authors.lastname: Colapinto
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: P A
authors.initials: PA
authors.lastname: Humphrey
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: D E
authors.initials: DE
authors.lastname: Bullard
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000276:immunology* / Q000532:radiotherapy; D005910:Glioma / Q000276:immunology* / Q000532:radiotherapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude / Q000276:immunology*; D009368:Neoplasm Transplantation; D011829:Radiation Dosage; D011878:Radiotherapy / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments