1 Biomedical Research Department, Centro Uruguayo de Imagenologia Molecular , Montevideo, Uruguay .
2 Department of Radiopharmacy, Centro Uruguayo de Imagenologia Molecular , Montevideo, Uruguay .
Cancer Biother Radiopharm. 2017 Nov;32(9):344-350. doi: 10.1089/cbr.2017.2334.
To compare the uptake of C-deuterodeprenyl (C-DED) and C-methionine (C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies.
Binding and internalization studies of C-MET and C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells. Immunofluorescence was used.
C-MET specific activity bound to membrane was 9.0%-11.1% and that internalized was 88.9%-91.0%. C-DED specific activity bound to membrane was 34.8%-58.0% and that internalized was 38.7%-65.2%. Immunocytochemistry revealed GFAP and MAO B expression.
The expression of MAO B measured by C-DED uptake or immunocytochemistry was not significantly different in grade III or IV cells. The GFAP signal was higher for grade IV compared to grade III. C-MET uptake was high in all the tumor cells. C-DED is a dopamine analogue and the transport across cell membranes is expected to be mediated by DAT receptors present in astrocytes. Reactive astrocytes surround tumor lesions; so the authors suggest that the C-DED uptake might be caused by the reactive astrocytosis and not by MAO B expression in tumor cells.
比较三种人神经胶质瘤细胞系对 C-氘代Deprenyl（C-DED）和 C-蛋氨酸（C-MET）的摄取，并研究其与神经胶质纤维酸性蛋白（GFAP）和单胺氧化酶 B（MAO B）表达的关系。C-DED 用于正电子发射断层扫描成像，作为各种中枢神经系统疾病中星形胶质细胞增生的标志物。它不可逆地与 MAO B 结合，MAO B 是一种胶质二聚酶，在一些神经病理学中活性增加。
在星形细胞瘤 3 级、胶质母细胞瘤 4 级和放射抗性胶质母细胞瘤 4 级细胞中进行 C-MET 和 C-DED 的结合和内化研究。采用免疫荧光法。
C-MET 结合到膜上的特异性活性为 9.0%-11.1%，内化的特异性活性为 88.9%-91.0%。C-DED 结合到膜上的特异性活性为 34.8%-58.0%，内化的特异性活性为 38.7%-65.2%。免疫细胞化学显示 GFAP 和 MAO B 的表达。
通过 C-DED 摄取或免疫细胞化学测量的 MAO B 表达在 3 级或 4 级细胞中没有显著差异。与 3 级相比，4 级的 GFAP 信号更高。所有肿瘤细胞的 C-MET 摄取都很高。C-DED 是一种多巴胺类似物，预计其跨细胞膜的转运将由星形胶质细胞中存在的 DAT 受体介导。反应性星形胶质细胞围绕肿瘤病变；因此，作者认为 C-DED 的摄取可能是由反应性星形胶质细胞增生引起的，而不是肿瘤细胞中 MAO B 的表达引起的。
