Black K L, Ikezaki K, Santori E, Becker D P, Vinters H V
Department of Neurology, University of California Los Angeles Medical Center 90024.
Cancer. 1990 Jan 1;65(1):93-7. doi: 10.1002/1097-0142(19900101)65:1<93::aid-cncr2820650120>3.0.co;2-1.
Two types of benzodiazepine receptors have been identified in mammalian tissues: a central type which is localized to neuronal elements in the brain, and a peripheral type which is present on glial cells and in tissues outside the central nervous system such as kidney. The authors report an increase in specific binding of peripheral benzodiazepine receptor ligands in certain human brain tumors using computer assisted quantitative image analysis of autoradiograms. Higher densities of binding sites to a 3H-labeled selective peripheral benzodiazepine ligand, PK11195 [1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] were observed in human gliomas as the malignancy of these tumors increased. Specific binding was also present in some non-glial tumors but little binding was demonstrated in necrotic tissue or normal brain. In in vitro binding studies in rats, there was a significant increase in Bmax (1089.3 +/- 232.2 fmol/mg tissue) in C6 glial tumors and LK Walker 256 metastatic tumors (924.2 +/- 183.7) compared with normal brain (62.1 +/- 12.8 fmol/mg tissue). Binding affinities were, however, similar (Kd = 2.09, 2.17, and 2.04 nmol/l, respectively). These findings suggest that the number of peripheral benzodiazepine receptors are increased in brain tumors. These receptors could be utilized in positron emission tomography to image brain tumors.
在哺乳动物组织中已鉴定出两种类型的苯二氮䓬受体：一种是中枢型，定位于大脑中的神经元成分；另一种是外周型，存在于胶质细胞以及中枢神经系统以外的组织如肾脏中。作者通过对放射自显影片进行计算机辅助定量图像分析，报告了某些人类脑肿瘤中外周苯二氮䓬受体配体的特异性结合增加。随着这些肿瘤恶性程度的增加，在人类胶质瘤中观察到对3H标记的选择性外周苯二氮䓬配体PK11195[1-(2-氯苯基)-N-甲基-N-(1-甲基丙基)-3-异喹啉甲酰胺]的结合位点密度更高。在一些非胶质肿瘤中也存在特异性结合，但在坏死组织或正常脑组织中几乎没有结合。在大鼠的体外结合研究中，与正常脑（62.1±12.8 fmol/mg组织）相比，C6胶质肿瘤和LK Walker 256转移瘤（924.2±183.7）中的Bmax（最大结合容量）显著增加（1089.3±232.2 fmol/mg组织）。然而，结合亲和力相似（解离常数分别为2.09、2.17和2.04 nmol/l）。这些发现表明脑肿瘤中外周苯二氮䓬受体的数量增加。这些受体可用于正电子发射断层扫描以对脑肿瘤进行成像。
