Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting.
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 10x greater than that of the isotype control mAb and 20x 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.
Paul
Asit K
AK
Department of Nuclear Medicine, School of Medicine and Biomedical Sciences, State University of New York, University at Buffalo, Buffalo, NY, USA.
Ciesielski
Michael J
MJ
Sajjad
Munawwar
M
Wang
Xinhui
X
Ferrone
Soldano
S
Abdel-Nabi
Hani
H
Fenstermaker
Robert A
RA
D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000378:metabolism*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D011509:Proteoglycans / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D000099216:Chondroitin Sulfate Proteoglycan 4
D000911:Antibodies, Monoclonal; D000941:Antigens; D007457:Iodine Radioisotopes; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C088548:IMMT protein, human