Chandra Rajesh, Oya Shunichi, Kung Mei-Ping, Hou Catherine, Jin Lee-Way, Kung Hank F
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Med Chem. 2007 May 17;50(10):2415-23. doi: 10.1021/jm070090j. Epub 2007 Apr 21.
A series of 18F fluoropegylated diphenylacetylenes as probes for binding to Abeta plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (Ki 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 [18F]12a, 12b, 14a, and 14b, respectively). [18F]12b and [18F]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, [18F]12a and [18F]14a (1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to Abeta plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of Abeta plaques in the brain of patients with Alzheimer's disease.
成功制备了一系列作为与β淀粉样蛋白斑结合探针的18F氟代聚乙二醇化二苯乙炔。这些相对刚性的乙炔化合物12a、12b、14a和14b，在死后的阿尔茨海默病脑匀浆中表现出高结合亲和力（Ki范围为1.2至2.9 nM）。正常小鼠体内的生物分布显示出优异的初始脑摄取率（在2分钟时，[18F]12a、12b、14a和14b的脑摄取率分别为4.42%、4.55%、5.41%和6.78%剂量/克）。具有较长氟代聚乙二醇化单元（即n = 3）的[18F]12b和[18F]14b，与较短氟代聚乙二醇化链配体（即[18F]12a和[18F]14a）相比，在注射后30分钟时脑清除更快（分别为0.42%和1.57%剂量/克，而[18F]12a和[18F]14a为1.03%和3.69%剂量/克）。放射自显影和匀浆结合证实了由于β淀粉样蛋白斑产生的高结合信号。这些初步结果表明，新型二苯乙炔可能对阿尔茨海默病患者大脑中的β淀粉样蛋白斑成像具有潜在用途。
