Department of Radiation Oncology, University of Washington, Seattle, WA 98105, USA.
Nucl Med Biol. 2010 Feb;37(2):167-78. doi: 10.1016/j.nucmedbio.2009.10.004.
In vivo deastatination of (211)At-labeled biomolecules can severely limit their use in endoradiotherapy. Our studies have shown that the use of closo-decaborate(2-) moiety for (211)At-labeling of biomolecules provides high in vivo stability towards deastatination. However, data from those studies have also been suggestive that some astatinated closo-decaborate(2-) catabolites may be retained in tissues. In this study, we investigated the in vivo distributions of several structurally simple closo-decaborate(2-) derivatives to gain information on the effects of functional groups if catabolites are released into the blood system from the carrier biomolecule.
Thirteen closo-decaborate(2-) derivatives were synthesized and radioiodinated for evaluation. Tissue concentrations of the radioiodinated compounds were obtained in groups of five mice at 1 and 4 h postinjection (pi). Dual-label ((125)I and (131)I) experiments permitted evaluation of two compounds in each set of mice.
All of the target compounds were readily synthesized. Radioiodination reactions were conducted with chloramine-T and Na[(125/131)I]I in water to give high yields (75-96%) of the desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites released into the blood system) showed small differences in tissue concentrations for some compounds, but large differences for others. The results indicate that formal (overall) charge on the compounds could not be used as a predictor of tissue localization or retention. However, derivatives containing carboxylate groups generally had lower tissue concentrations. Acid cleavable hydrazone functionalities appeared to be the best candidates for further study.
Further studies incorporating hydrazone functionalities into pendant groups for biomolecule radiohalogenation are warranted.
体内去砜化（211）At 标记的生物分子会严重限制它们在放射性核素内照射治疗中的应用。我们的研究表明，使用 closo-癸硼烷（2-）部分为生物分子进行（211）At 标记可提供针对去砜化的高体内稳定性。然而，这些研究的数据也表明，一些被 astatinated 的 closo-癸硼烷（2-）代谢产物可能在组织中被保留。在这项研究中，我们研究了几种结构简单的 closo-癸硼烷（2-）衍生物的体内分布，以了解如果代谢产物从载体生物分子释放到血液系统中，官能团会产生什么影响。
合成了 13 种 closo-癸硼烷（2-）衍生物并进行放射性碘标记以进行评估。在注射后 1 小时和 4 小时，每组 5 只小鼠获得放射性标记化合物的组织浓度。双标记（（125）I 和（131）I）实验允许在每组小鼠中评估两种化合物。
所有目标化合物都很容易合成。用氯胺-T 和 Na[(125/131)I]I 在水中进行放射性碘标记反应，以获得所需化合物的高收率（75-96%）。注射后 1 小时和 4 小时的生物分布数据（代表释放到血液系统中的代谢产物）显示，一些化合物的组织浓度差异较小，但其他化合物的差异较大。结果表明，化合物的总形式电荷不能用作组织定位或保留的预测指标。然而，含有羧酸盐基团的衍生物通常具有较低的组织浓度。酸可裂解的腙官能团似乎是进一步研究的最佳候选物。
进一步的研究将腙官能团整合到生物分子放射性卤化的侧链基团中是有必要的。
