The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.
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.
Colapinto
E V
EV
Department of Pathology, Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, North Carolina 27710.
Lee
Y S
YS
Humphrey
P A
PA
Zalutsky
M R
MR
Friedman
H S
HS
Bullard
D E
DE
Bigner
D D
DD
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
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments