Serdons K, Verduyckt T, Cleynhens J, Terwinghe C, Mortelmans L, Bormans G, Verbruggen A
Laboratory for Radiopharmacy, K.U. Leuven, Leuven, Belgium.
Bioorg Med Chem Lett. 2007 Nov 15;17(22):6086-90. doi: 10.1016/j.bmcl.2007.09.055. Epub 2007 Sep 18.
We have conjugated S,S'-bis-trityl-N-BOC-N'-acetic acid-1,2-ethylenedicysteamine, a protected bis-amino-bis-thiol (BAT) tetraligand, with 2-(4'-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with (99m)Tc by heating of the protected precursor in diluted hydrochloric acid followed by neutralization and heating in the presence of (99m)Tc-tartrate. It was demonstrated that the (99m)Tc-BAT-phenylbenzothiazole conjugate binds in vitro to amyloid beta present in postmortem brain slices of Alzheimer's patients. Despite its high lipophilicity and neutral character, the radiolabelled conjugate did not cross the blood-brain barrier to a sufficient degree and therefore is not useful for detection of Alzheimer's disease. Further evaluation of this (99m)Tc-labelled tracer agent could elucidate its potential usefulness to visualize amyloid plaques in peripheral amyloidosis.
我们已将S,S'-双三苯基-N-叔丁氧羰基-N'-乙酸-1,2-乙二硫胺（一种受保护的双氨基双硫醇（BAT）四配体）与2-(4'-氨基苯基)-1,3-苯并噻唑（硫黄素-T的衍生物，对淀粉样蛋白具有已知亲和力）进行共轭。通过在稀盐酸中加热受保护的前体，然后中和并在(99m)Tc-酒石酸盐存在下加热，使共轭物有效地用(99m)Tc标记。结果表明，(99m)Tc-BAT-苯基苯并噻唑共轭物在体外与阿尔茨海默病患者死后脑切片中存在的淀粉样β蛋白结合。尽管其具有高亲脂性和中性特征，但放射性标记的共轭物并未充分穿过血脑屏障，因此对阿尔茨海默病的检测无用。对这种(99m)Tc标记的示踪剂进行进一步评估，可能会阐明其在外周淀粉样变性中可视化淀粉样斑块的潜在用途。
