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.

中文翻译：

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DOTA-ZOL：骨转移诊断和姑息治疗的有前景的工具——临床常规实施中的挑战和关键点

新型化合物 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸 (DOTA)-ZOL（DOTA-共轭唑来膦酸）是诊断和治疗骨转移的有希望的候选者。这种双膦酸盐的已发表方法与药物和监管要求相结合，结果出乎意料地具有挑战性。这项工作的范围是介绍和讨论此过程中遇到的问题。简而言之，放射性标记过程和纯化，以及公布的质量控制，没有达到预期。建立自动放射性标记程序的不断努力导致（a）使用涂层玻璃反应器的增强的手动方法，(b) 三种不同的可靠无线电薄层色谱 (TLC) 方法的组合，而不是已发表的方法和 (c) 一种初步的无线电高压液相色谱 (HPLC) 方法，用于鉴定化合物。此外，还开发了自动放射性标记过程，但它需要进一步改进，例如，在反应器容器或粗产物纯化方面。发现公开的纯化方法不适合临床常规，密集筛选未得到满意结果；在这里，需要更多的研究。综上所述，DOTA-ZOL 的实施是可能的，但揭示了很多关键点，其中并非所有都可以完全解决。开发了一种自动放射性标记过程，但它需要进一步改进，例如，在反应器容器或粗产品纯化方面。发现公开的纯化方法不适合临床常规，密集筛选未得到满意结果；在这里，需要更多的研究。综上所述，DOTA-ZOL 的实施是可能的，但揭示了很多关键点，其中并非所有都可以完全解决。开发了一种自动放射性标记过程，但它需要进一步改进，例如，在反应器容器或粗产品纯化方面。发现公开的纯化方法不适合临床常规，密集筛选未得到满意结果；在这里，需要更多的研究。综上所述，DOTA-ZOL 的实现是可能的，但暴露了很多关键点，其中还不是所有的都可以完全解决。