Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts 02142, USA.
Bioconjug Chem. 2009 Aug 19;20(8):1625-33. doi: 10.1021/bc900192b. Epub 2009 Jul 2.
Technetium tricarbonyl chemistry has been a subject of interest in radiopharmaceutical development over the past decade. Despite the extensive work done on developing chelates for Tc(I), a rigorous investigation of the impact of changing donor groups and labeling conditions on radiochemical yields and/or distribution has been lacking. This information is crucially important if these platforms are going to be used to develop molecular imaging probes. Previous studies on the coordination chemistry of the {M(CO)(3)}(+) core have established alkylamine, aromatic nitrogen heterocycles, and carboxylate donors as effective chelating ligands. These observations led to the design of tridentate ligands derived from the amino acid lysine. Such amino acid analogues provide a tridentate donor set for chelation to the metal and an amino acid functionality for conjugation to biomolecules. We recently developed a family of single amino acid chelates (SAAC) that serve this function and can be readily incorporated into peptides via solid-phase synthesis techniques. As part of these continuing studies, we report here on the radiolabeling with technetium-99m ((99m)Tc) and stability of a series of SAAC analogues of lysine. The complexes studied include cationic, neutral, and anionic complexes. The results of tissue distribution studies with these novel complexes in normal rats demonstrate a range of distribution in kidney, liver, and intestines.
在过去的十年中，锝三羰基化学一直是放射性药物开发的研究课题。尽管已经对 Tc(I) 的螯合物进行了广泛的研究，但对于改变供体基团和标记条件对放射化学产率和/或分布的影响，还缺乏严格的研究。如果这些平台将被用于开发分子成像探针，那么这些信息至关重要。先前关于{M(CO)(3)}（+）核心配位化学的研究已经确定了烷基胺、芳族氮杂环和羧酸盐供体是有效的螯合配体。这些观察结果导致了从氨基酸赖氨酸衍生的三齿配体的设计。这些氨基酸类似物为螯合金属提供了一个三齿供体组，并为与生物分子的缀合提供了氨基酸功能。我们最近开发了一系列单氨基酸螯合物（SAAC），它们具有这种功能，并且可以通过固相合成技术很容易地掺入到肽中。作为这些持续研究的一部分，我们在这里报告了一系列赖氨酸的 SAAC 类似物的锝-99m（(99m)Tc）放射性标记和稳定性。所研究的配合物包括阳离子、中性和阴离子配合物。这些新型配合物在正常大鼠中的组织分布研究结果表明，其在肾脏、肝脏和肠道中的分布范围不同。
