Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting
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Human melanoma proteoglycan (HMP), a melanoma-associated antigen, is expressed in both human melanomas and gliomas. We used HMP-specific monoclonal antibody (mAb) VT68.2 to investigate whether murine GL261 cerebral gliomas express the HMP homologue AN2 and to determine whether AN2 could be targeted for selective delivery of radiation in vivo. HMP-specific mAb VT68.2 stained murine GL261 glioma cells grown in culture and intracerebrally in syngeneic C57BL/6 mice. Positron emission tomography with radiolabeled mAb VT68.2 showed high-contrast, positive images of gliomas against a negative background. At 96 h after injection, glioma uptake of radiolabeled mAb VT68.2 was 10× greater than that of the isotype control mAb and 20× greater than that detected in normal cerebral tissue. Our results show murine GL261 cerebral gliomas express AN2 and HMP-specific mAb VT68.2 accumulates selectively and specifically at high concentration and is retained within murine cerebral gliomas. Thus, HMP is a potential target for antibody-mediated selective delivery of radiation to cerebral gliomas in vivo.
KeywordsRadioimmunotargeting Glioma Human melanoma proteoglycan (HMP) microPET Monoclonal antibodies
This work was supported in part by research grants NS049309 awarded to RAF by the National Institute of Neurological Disorders and Stroke (NIH/NINDS) and CA105500 awarded to SF by the National Cancer Institute. Additional support provided by the Roswell Park Cancer Institute Cancer Center Support Grant CA16056-29 (NIH-NCI), the Roswell Park Alliance Foundation and the Linda Scime Neurosurgery Endowment Fund. The authors would like to thank Rolf F. Barth, MD for his generous gift of GL261 glioma cells and John Luisi, CNMT for the assistance with microPET data acquisition.
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