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黑色素瘤相关抗原HMP/AN2在小鼠脑胶质瘤中的表达:放射免疫靶向治疗的潜力

Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting.

作者信息

Paul Asit K, Ciesielski Michael J, Sajjad Munawwar, Wang Xinhui, Ferrone Soldano, Abdel-Nabi Hani, Fenstermaker Robert A

机构信息

Department of Nuclear Medicine, School of Medicine and Biomedical Sciences, State University of New York, University at Buffalo, Buffalo, NY, USA.

出版信息

J Neurooncol. 2009 Aug;94(1):21-30. doi: 10.1007/s11060-009-9798-3. Epub 2009 Jan 20.

Abstract

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.

摘要

人黑色素瘤蛋白聚糖(HMP)是一种与黑色素瘤相关的抗原,在人黑色素瘤和神经胶质瘤中均有表达。我们使用HMP特异性单克隆抗体(mAb)VT68.2来研究小鼠GL261脑胶质瘤是否表达HMP同源物AN2,并确定AN2是否可作为体内辐射选择性递送的靶点。HMP特异性mAb VT68.2对培养的以及在同基因C57BL/6小鼠脑内生长的小鼠GL261胶质瘤细胞进行了染色。用放射性标记的mAb VT68.2进行正电子发射断层扫描显示,在阴性背景下胶质瘤呈现高对比度的阳性图像。注射后96小时,放射性标记的mAb VT68.2在胶质瘤中的摄取量比同型对照单克隆抗体高10倍,比正常脑组织中检测到的摄取量高20倍。我们的结果表明,小鼠GL261脑胶质瘤表达AN2,且HMP特异性mAb VT68.2在小鼠脑胶质瘤中选择性、特异性地高浓度聚集并保留。因此,HMP是体内抗体介导的向脑胶质瘤选择性递送辐射的潜在靶点。

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