New diphenylacetylenes as probes for positron emission tomographic imaging of amyloid plaques
New diphenylacetylenes as probes for positron emission tomographic imaging of amyloid plaques
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DOI：
10.1021/jm070090j
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发表时间：
2007-05-17
影响因子：
7.3
通讯作者：
Kung, Hank F.
中科院分区：
文献类型：
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作者：
Chandra, Rajesh;Oya, Shunichi;Kung, Hank F.
成功制备了一系列F-18氟聚乙二醇化二苯乙炔作为结合A β斑块的探针。这些相对刚性的乙炔12 a、12 b、14 a和14 b在死后AD脑匀浆中显示出高结合亲和力（Ki范围为1.2至2.9 nM）。在正常小鼠中的体内生物分布显示出极好的初始脑渗透率（[F-18] 12 a、12 b、14 a和14 b在2 min时分别为4.42、4.55、5.41和6.78%剂量/g）。[F-18] 12 b和[F-18] 14 b（具有较长的氟聚乙二醇化单元，即n = 3）在注射后30 min时显示出比较短的氟聚乙二醇化链配体（即[F-18] 12 a和[F-18] 14 a（1.03和3.69%剂量/g））更快的脑洗脱（0.42和1.57%剂量/g）。放射自显影和匀浆结合证实了A β斑块引起的高结合信号。这些初步结果表明，新的二苯基乙炔可能是潜在的有用的阿尔茨海默病患者的大脑中的A β斑块的成像。
A series of F-18 fluoropegylated diphenylacetylenes as probes for binding to A beta plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (K-i ranging from 1.2 to 2.9 nM). In vivo biodistribution in normal mice exhibited excellent initial brain penetrations (4.42, 4.55, 5.41, and 6.78% dose/g at 2 min for [F-18]12a, 12b, 14a, and 14b, respectively). [F-18]12b and [F-18]14b, with a longer fluoropegylated unit, that is, n = 3, showed faster brain washout at 30 min postinjection (0.42 and 1.57% dose/g) as compared to the shorter fluoropegylated chain ligands, that is, [F-18]12a and [F-18]14a(1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to A beta plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of A beta plaques in the brain of patients with Alzheimer's disease.