DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis-Challenges and Critical Points in Implementation into Clinical Routine
DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis-Challenges and Critical Points in Implementation into Clinical Routine
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DOI：
10.3390/molecules25132988
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Eppard, Elisabeth
中科院分区：
文献类型：
--
作者：
Meisenheimer, Michael;Kuerpig, Stefan;Eppard, Elisabeth
新化合物1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸（DOTA）-ZOL（DOTA-conjugated zoledronic acid）在骨转移癌的诊断和治疗方面具有广阔的应用前景。事实证明，将已发表的这种双膦酸盐方法与制药和监管要求相结合具有意想不到的挑战性。这项工作的范围是介绍和讨论在这一过程中遇到的问题。简言之，放射性标记工艺和纯化以及已发表的质量控制不符合预期。建立自动化放射性标记程序的持续努力导致（a）使用涂层玻璃反应器的增强型手动方法，（B）三种不同可靠的放射性薄层色谱（TLC）方法的组合，而不是已发表的方法，以及（c）用于鉴定化合物的初步放射性高压液相色谱（HPLC）方法。此外，开发了自动化放射性标记过程，但需要进一步改进，例如，就反应器容器或粗产物的纯化而言。已发表的纯化方法被发现不适合临床常规，并且密集的筛选没有得到令人满意的结果;在这里，需要进行更多的研究。综上所述，DOTA-ZOL的实施是可能的，但也暴露了很多关键点，其中并不是所有的问题都可以完全解决。
The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process. Briefly, the radiolabelling process and purification, as well as the quality control published, did not meet the expectations. The constant effort setting up an automated radiolabelling procedure resulted in (a) an enhanced manual method using coated glass reactors, (b) a combination of three different reliable radio thin-layer chromatography (TLC) methods instead of the published and (c) a preliminary radio high-pressure liquid chromatography (HPLC) method for identification of the compound. Additionally, an automated radiolabelling process was developed, but it requires further improvement, e.g., in terms of a reactor vessel or purification of the crude product. The published purification method was found to be unsuitable for clinical routine, and an intense screening did not lead to a satisfactory result; here, more research is necessary. To sum up, implementation of DOTA-ZOL was possible but revealed a lot of critical points, of which not all could be resolved completely yet.