In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET
In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET
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DOI：
10.1093/brain/aww098
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发表时间：
2016-07-01
期刊：
影响因子：
14.5
通讯作者：
Borghammer, Per
中科院分区：
文献类型：
--
作者：
Hansen, Allan K.;Knudsen, Karoline;Borghammer, Per
tau缠结配体F-18-AV-1451（F-18-T807）与中脑中的神经黑色素结合，因此可能是黑质中色素多巴胺能神经元计数的量度。帕金森病的特征在于多巴胺能神经元的进行性丧失。尸检数据的外推预测，黑质多巴胺神经元的类似30%的下降是导致帕金森病运动症状所必需的。疾病发作时的壳核多巴胺终末损失最有可能超过黑质细胞体的损失，估计为50- 70%的量级。我们研究了F-18-AV-1451正电子发射断层扫描可视化帕金森病黑质神经黑色素浓度的实用性，并将结果与I-123-FP-CIT单光子发射计算机断层扫描测量的多巴胺转运蛋白密度相关。共有17例原发性帕金森病患者和16例年龄和性别匹配的对照受试者使用西门子高分辨率研究断层扫描仪进行F-18-AV-1451正电子发射断层扫描。12例帕金森病患者也在我们的成像设施接受了标准化I-123-FP-CIT单光子发射计算机断层扫描。许多帕金森病患者在中脑中显示出视觉上明显的F-18-AV-1451信号降低。定量时，与对照组相比，患者显示总黑质F-18-AV-1451分布容积平均降低30%（P = 0.004），但个体范围重叠。我们没有看到症状优势侧和对侧黑质分布体积之间的显着相关性。黑质F-18-AV-1451分布容积与年龄或自诊断以来的时间无关。在12例患者亚组中，也进行了I-123-FP-CIT扫描，在中位疾病持续时间为4.7年（0.5-12.4年）后，平均总纹状体多巴胺转运蛋白信号降低了45%，平均总F-18-AV-1451黑质分布体积降低了33%。F-18-AV-1451正电子发射断层扫描可能是第一个反映帕金森病患者黑质色素神经元丢失的放射性示踪剂。黑质信号丢失的幅度小于多巴胺转运蛋白单光子发射计算机断层扫描测量的纹状体多巴胺转运蛋白信号的减少。这些研究结果表明，更严重的损失纹状体神经末梢功能相比，神经元细胞体，根据尸检文献。
The tau tangle ligand F-18-AV-1451 (F-18-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a similar to 30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of F-18-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by I-123-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had F-18-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized I-123-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased F-18-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral F-18-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral F-18-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a I-123-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total F-18-AV-1451 substantia nigra volume of distribution was decreased by 33% after median disease duration of 4.7 years (0.5-12.4 years). F-18-AV-1451 positron emission tomography may be the first radiotracer to reflect the loss of pigmented neurons in the substantia nigra of parkinsonian patients. The magnitude of the nigral signal loss was smaller than the decrease in striatal dopamine transporter signal measured by dopamine transporter single photon emission computed tomography. These findings suggest a more severe loss of striatal nerve terminal function compared with neuronal cell bodies, in accordance with the post-mortem literature.