The type III mutant
epidermal growth factor receptor (EGFR) is expressed on the cell surface of a subset of
glioma, but not of normal tissues. In this study, we investigated the in vivo kinetics of 3C10 mouse
monoclonal antibody (mAb), specifically recognizing the type III mutant EGFR (
EGFRvIII), using athymic nude mice bearing the intracranial
glioma xenograft overexpressing the
EGFRvIII. Human
glioma cell line, U87MG, expressing the wild type EGFR and the transfectant, named U87MG x deltaEGFR, expressing the
EGFRvIII, were transplanted subcutaneously or intracranially to nude mice. 3C10 mAb labeled with a technetium-99m (99mTc) was intravenously injected into these nude mice and then the mice were sacrificed at 24 h later, and the 99mTc-uptake by xenografts and major normal organs was measured to determine the biodistribution of mAb. Furthermore, at 3, 6 and 24 h after injection of 99mTc-labeled 3C10 mAb, whole-body scintigraphy was obtained with a
gamma camera to localize the
tumor site. 3C10 mAb significantly accumulated to U87MG x deltaEGFR xenografts transplanted subcutaneously or intracranially in nude mice, showing high
tumor-to-blood ratio of 10.30 and 4.01, respectively. In contrast, uptake of control antibody in the intracranial
tumor was as low as 0.43. In scintigrams, intracranially transplanted U87MG x deltaEGFR xenografts were detectable at 3 h after injection of 99mTc-labeled 3C10 mAb. These results suggest that intravenously injected 3C10 mAb specifically accumulated to the subcutaneous or intracranial
glioma xenograft expressing the
EGFRvIII and 3C10 mAb is a potential diagnostic and therapeutic agent for patients with
gliomas expressing the
EGFRvIII.