A tributyltin precursor was synthesized through a 5-step reaction from 2-amino-6-bromobenzothiazole, and [125I]1 was synthesized by an iododestannylation reaction with a tributyltin precursor. Mouse models of amyloid A (AA) amyloidosis, a type of systemic amyloidosis, were prepared by intraperitoneal injection of amyloid-enhancing factor into mice. An in vitro autoradiographic study was performed using spleen sections from normal mice and AA amyloidosis mice. Furthermore, [125I]1 was intravenously injected into mice, and its distribution was evaluated. Finally, an ex vivo autoradiographic study was performed using AA amyloidosis mice.
[125I]1 was obtained with a radiochemical yield of 66% and a radiochemical purity of over 95%. In vitro autoradiography revealed specific binding of [125I]1 to thioflavin-S-stained regions in the spleen. Normal mice showed relatively rapid clearance of [125I]1 from the organs, whereas radioactivity was retained in the spleen, where amyloid deposition was observed in model mice. Furthermore, ex vivo autoradiography showed a heterogeneous distribution of [125I]1, which was co-localized with thioflavin-S-stained regions in the spleen of model mice.
These results indicate the potential of radioiodinated 1 as a nuclear imaging probe for diagnosing AA amyloidosis.
由2-氨基-6-溴苯并噻唑通过5步反应合成了三丁基锡前体,[125I]1是通过与三丁基锡前体的碘去锡烷基化反应合成的。淀粉样蛋白A(AA)淀粉样变性小鼠模型,一种系统性淀粉样变性,通过向小鼠腹腔注射淀粉样蛋白增强因子制备。使用正常小鼠和AA淀粉样变性小鼠的脾切片进行体外放射自显影研究。此外,[125I]1静脉注射给小鼠,并对其分布进行了评估。最后,使用AA淀粉样变性小鼠进行离体放射自显影研究。
以66%的放射化学产率和超过95%的放射化学纯度获得[125I]1。体外放射自显影显示[125I]1与脾脏中硫黄素-S染色区域的特异性结合。正常小鼠从器官中清除[125I]1相对较快,而放射性保留在脾脏中,在模型小鼠中观察到淀粉样蛋白沉积。此外,离体放射自显影显示[125I]1的不均匀分布,与模型小鼠脾脏中的硫黄素S染色区域共定位。
这些结果表明放射性碘化1作为诊断AA淀粉样变性核成像探针的潜力。