Abstract：
Systemic amyloidosis is a group of diseases characterized by the deposition of amyloid protein in multiple organs throughout the body and causing their dysfunction. As amyloid deposition is observed at an early phase and is highly specific to systemic amyloidosis, noninvasive detection of amyloid is considered useful for the early diagnosis of systemic amyloidosis. In this study, we designed and synthesized a novel radiolabeled amyloid imaging probe, sodium (E)-4-amino-3-((4-(6-iodobenzothiazol-2-yl)phenyl)diazenyl)naphthalene-1-sulfonate (1), which combines two amyloid-binding compounds, thioflavin-T and Congo-red, and evaluated its effectiveness in diagnosing amyloidosis.
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.
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.
摘要：
系统性淀粉样变性是一组以淀粉样蛋白在全身多个器官中沉积并导致其功能障碍为特征的疾病。由于淀粉样蛋白沉积是在早期阶段观察到的，并且对系统性淀粉样变性具有高度特异性，无创性检测淀粉样蛋白被认为有助于系统性淀粉样变性的早期诊断。在这项研究中,我们设计并合成了一种新型的放射性标记淀粉样蛋白成像探针，(E)-4-氨基-3-((4-(6-碘苯并噻唑-2-基)苯基)二氮烯基)萘-1-磺酸钠(1)，结合了两种淀粉样蛋白结合化合物，硫黄素-T和刚果红，并评估其诊断淀粉样变性的有效性。
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。
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。
