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Novel receptor-targeted contrast agents for optical imaging of tumors

机译：用于肿瘤光学成像的新型受体靶向造影剂

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Abstract: Many gastroenteropancreatic tumors express receptors for somatostatin (SST) and/or vasoactive intestinal peptide (VIP). These receptors can be used as molecular targets for the delivery of contrast agents for tumor diagnostics. We have synthesized conjugates consisting of a cyanine dye and an SST analogue or VIP for use as contrast agents in optical imaging. Receptor binding and internalization of these compounds were examined with optical methods in transfected RIN38 tumor cells expressing the SST2 receptor or a GFP- labeled VIP (VPAC1) receptor. Furthermore, biodistribution of the conjugates was examined by laser-induced fluorescence imaging in nude mice bearing SST2 or VPAC1 receptor- expressing tumors. After incubation of RIN38 SSTR2 cells in the presence of 100 nM indotricarbocyanine-SST analogue, cell-associated fluorescence increased, whereas no increase was observed when receptor-medicated endocytosis was inhibited. Indodicarbocyanine-VIP accumulated in RIN38 VPAC1 cells and co-localization with the GFP-labeled VPAC1 receptor was observed. After injection of indotricarbocyanine-SST analogue into tumor-bearing nude mice, SST2 receptor-positive tumors could be visualized for a time period from 10 min to at least 48 h. After application of indodicarbocyanine-VIP, a fluorescence signal in VIP1 receptor-expressing tumors was only detected during the first hour. We conclude that cyanine dye-labeled VIP and SST analogue are novel, targeted contrast agents for the optical imaging of tumors expressing the relevant receptor.!26
机译：摘要：许多胃肠胰腺肿瘤表达生长抑素（SST）和/或血管活性肠肽（VIP）的受体。这些受体可以用作递送用于肿瘤诊断的造影剂的分子靶标。我们合成了由花菁染料和SST类似物或VIP组成的共轭物，用作光学成像中的造影剂。在表达SST2受体或GFP标记的VIP（VPAC1）受体的转染RIN38肿瘤细胞中，用光学方法检查了这些化合物的受体结合和内在化。此外，在带有SST2或VPAC1受体表达肿瘤的裸鼠中，通过激光诱导的荧光成像检查了缀合物的生物分布。在100 nM吲哚三聚氰胺-SST类似物存在下温育RIN38 SSTR2细胞后，细胞相关的荧光增加，而受体治疗的内吞作用被抑制时则未见增加。观察到吲哚碳花青-VIP积累在RIN38 VPAC1细胞中，并与GFP标记的VPAC1受体共定位。向患有肿瘤的裸鼠注射吲哚三聚氰胺-SST类似物后，可以观察到SST2受体阳性肿瘤的时间为10分钟至至少48小时。施用吲哚并二甲花菁-VIP后，仅在第一个小时内检测到表达VIP1受体的肿瘤中的荧光信号。我们得出结论，花青染料标记的VIP和SST类似物是新颖的，靶向的造影剂，用于表达相关受体的肿瘤的光学成像。26

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