title: Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts.
abstract: Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to normal tissues. In this study, we have examined the in vivo localization of radioiodinated MAb Me1-14, a murine immunoglobulin G2a (IgG2a) reactive with gliomas, and its F(ab')2 fragment in s.c. and intracranial xenografts of human glioma cell line D-54 MG in athymic mice. The radiolabeled F(ab')2 fragment of Me1-14 was demonstrated to possess in vitro binding affinity and immunoreactivity comparable to that of whole IgG. Direct comparison of IgG and F(ab')2 biodistribution in s.c. xenograft-bearing mice showed higher tumor: normal tissue ratios of the F(ab')2 fragment compared to IgG. In intracranial tumor-bearing mice paired-label analysis using a nonspecific protein control showed earlier specific tumor localization by the F(ab')2 fragment of Me1-14 compared to IgG. Blood-to-tumor transfer constants (K1) derived for Me1-14 F(ab')2 were significantly greater than those for whole Me1-14 (P = 0.01). Estimated radiation dosimetry revealed that 131I-labeled Me1-14 F(ab')2 would deliver higher radiation doses to tumor than to normal tissues. These studies demonstrate that the F(ab')2 fragment of Me1-14 may be a potential agent for immune-directed brain tumor diagnosis and therapy.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: E V
authors.initials: EV
authors.lastname: Colapinto
authors.forename: P A
authors.initials: PA
authors.lastname: Humphrey
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: D R
authors.initials: DR
authors.lastname: Groothuis
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: N
authors.initials: N
authors.lastname: de Tribolet
authors.forename: S
authors.initials: S
authors.lastname: Carrel
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D002460:Cell Line; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G