High-yielding aqueous 18F-labeling of peptides via Al18F chelation.

High-yielding aqueous 18F-labeling of peptides via Al18F chelation.
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DOI:
10.1021/bc200175c
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发表时间:
2011-09-21
影响因子:
4.7
通讯作者:
Goldenberg, David M.
Goldenberg, David M.
中科院分区:
化学2区
文献类型:
--
作者:
D'Souza, Christopher A.;McBride, William J.;Sharkey, Robert M.;Todaro, Louis J.;Goldenberg, David M.

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研究了一种以甲基苯乙酸(MPAA)为主链的新型五齿双功能络合剂Noda-MPAA 1的配位化学及其形成稳定Al18F-络合物的能力。有机氟铝酸盐很容易从1和AlF3的反应中得到。X射线衍射研究表明,铝位于一个轻微扭曲的八面体的中心,氟占据了其中一个轴向位置。叔丁基保护的螯合剂7可一步合成,可用于固相或溶液中偶联生物分子。肿瘤靶向多肽4与1共价连接,在10-15分钟内实现了高产率(55-89%)的18F-水溶液标记。在37℃的人血清中,至少4小时没有观察到脱氟。这些结果表明,将BFC-1作为一种通用的标记方法,可以方便地应用于放射氟化其他热稳定性多肽的正电子发射成像。
The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methyl phenyl acetic acid (MPAA) backbone, and its ability to form stable Al18F-chelates, was investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF3. X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55–89%) aqueous 18F-labeling was achieved in 10–15 minutes with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al18F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.
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