Evaluation of (99m)Tc-probestin SPECT as a novel technique for noninvasive imaging of kidney aminopeptidase N expression.
Evaluation of (99m)Tc-probestin SPECT as a novel technique for noninvasive imaging of kidney aminopeptidase N expression.
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DOI：
10.1021/mp5002872
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发表时间：
2014-08-04
影响因子：
4.9
通讯作者：
Gali H
中科院分区：
文献类型：
--
作者：
Pathuri G;Madka V;Hedrick AF;Lightfoot SA;Awasthi V;Cowley BD Jr;Rao CV;Gali H
氨基肽酶 N（APN；CD13；EC 3.4.11.2）是一种锌依赖性膜结合外肽酶，可催化从肽中去除 N 末端氨基酸。已知 APN 在肾皮质近曲小管上高表达。在肾毒素的影响下以及在肾癌的肿瘤区域中APN表达水平显着降低。因此，肾脏 APN 表达的分子成像可以无创地提供有关肾脏的病理生理学信息。 Probestin 是一种有效的 APN 抑制剂并与 APN 结合。注射 99mTc-probestin 1 小时后，对 12 只 UPII-SV40T 转基因和野生型小鼠进行腹部 SPECT 成像。 UPII-SV40T 小鼠自发发生原位尿路上皮癌和侵入肾脏的侵袭性移行细胞癌（TCC）。使用组织病理学和免疫组织化学分析来确认肿瘤的存在并评估肾脏中的 APN 表达。在 SPECT 图像中，肾皮质正常组织区域的放射性清晰可见，而肾皮质肿瘤区域的放射性吸收明显较低或没有。肾脏切片的组织病理学分析显示野生型小鼠的肾盂和皮质区域的形态正常，而一些转基因小鼠的形态异常。增殖细胞核抗原染色证实这些异常区域存在肿瘤。使用抗 CD13 抗体对肾脏切片进行免疫组织化学分析显示，与正常区域相比，肿瘤区域的 APN 表达显着降低。本研究获得的结果证明了 99mTc-probestin SPECT 作为肾脏 APN 表达无创成像新技术的潜在用途。
Aminopeptidase N (APN; CD13; EC 3.4.11.2) is a zinc-dependent membrane-bound exopeptidase that catalyzes the removal of N-terminal amino acids from peptides. APN is known to be highly expressed on renal cortical proximal tubules. APN expression levels are markedly decreased under the influence of nephrotoxins and in the tumor regions of renal cancers. Thus, molecular imaging of kidney APN expression could provide pathophysiological information about kidneys noninvasively. Probestin is a potent APN inhibitor and binds to APN. Abdominal SPECT imaging was conducted at 1 h postinjection of 99mTc-probestin in a group of 12 UPII-SV40T transgenic and wild-type mice. UPII-SV40T mice spontaneously develop urothelial carcinoma in situ and invasive transitional cell carcinoma (TCC) that invade kidneys. Histopathology and immunohistochemistry analysis were used to confirm the presence of tumor and to evaluate APN expression in kidney. Radioactivity in normal tissue regions of renal cortex was clearly visible in SPECT images, whereas tumor regions of renal cortex displayed significantly lower or no radioactivity uptake. Histopathological analysis of kidney sections showed normal morphology for both renal pelvic and cortical regions in wild-type mice and abnormal morphology in some transgenic mice. Proliferating cell nuclear antigen staining confirmed the presence of tumor in those abnormal regions. Immunohistochemical analysis of kidney sections using anti-CD13 antibody showed significantly lower APN expression in tumor regions compared to normal regions. Results obtained in this study demonstrate the potential use of 99mTc-probestin SPECT as a novel technique for noninvasive imaging of kidney APN expression.
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影响因子：
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作者：
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