Novel Bifunctional Cyclic Chelator for (89)Zr Labeling-Radiolabeling and Targeting Properties of RGD Conjugates.
Novel Bifunctional Cyclic Chelator for (89)Zr Labeling-Radiolabeling and Targeting Properties of RGD Conjugates.
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DOI：
10.1021/acs.molpharmaceut.5b00128
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发表时间：
2015-06-01
影响因子：
4.9
通讯作者：
Decristoforo, Clemens
中科院分区：
文献类型：
--
作者：
Zhai, Chuangyan;Summer, Dominik;Rangger, Christine;Franssen, Gerben M.;Laverman, Peter;Haas, Hubertus;Petrik, Milos;Haubner, Roland;Decristoforo, Clemens
在过去的几年中，89 Zr作为用于正电子发射断层扫描（PET）应用的长寿命放射性核素引起了相当大的关注。目前，去铁胺B（DFO）主要用作双功能螯合剂。Fusarinine C（FSC）具有与DFO相当的络合性质，由于其环状结构，预计将成为具有潜在更高稳定性的替代品。在这项研究中，作为原理的证明，使用不同的缀合策略合成了靶向α v β 3整联蛋白的各种FSC-RGD缀合物，并用89 Zr标记。使用[89 Zr]FSC-RGD缀合物或[89 Zr]三乙酰镰孢菌素C（TAFC）评价体外稳定性、生物分布和microPET/CT成像。在室温下在90分钟内实现定量89 Zr标记。不同放射性配体的分配系数表明亲水性。与[89 Zr]DFO相比，[89 Zr]FSC衍生物在磷酸盐缓冲盐水（PBS）、乙二胺四乙酸溶液（EDTA）和人血清中显示出优异的体外稳定性和对转螯合的耐受性长达7天。细胞结合研究和生物分布以及microPET/CT成像实验显示[89 Zr]FSC-RGD缀合物的有效受体特异性靶向。分析PET图像未观察到骨摄取，表明体内稳定性高。这些结果表明，FSC是一个非常有前途的螯合剂为基础的PET显像剂的发展。
Within the last years 89Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting αvß3 integrins were synthesized using different conjugation strategies and labeled with 89Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [89Zr]FSC-RGD conjugates or [89Zr]triacetylfusarinine C (TAFC). Quantitative 89Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [89Zr]DFO, [89Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [89Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of 89Zr-based PET imaging agents.
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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