An Instant Kit for 2-[18F]Fluoro-2-deoxyglucose (FDG)

描述（由申请人提供）：由于Hamacher等人开发了高产率亲核取代反应，并开发了用于一步或两步合成F-18标记靶分子的市售前体，因此开发了大量分子成像探针。对临床护理影响最大的放射性示踪剂是F-18 2-氟-2-脱氧葡萄糖（FDG）。然而，目前FDG和其他F-18标记探针的合成需要热室（或微型室）和复杂的多阀合成系统。使F-18放射性药物容易获得的最后一步是开发一种“试剂盒”，该试剂盒可以通过简单地将F-18氟化物加入小瓶中来生产F-18放射性药物，最多进行一次小柱纯化。通过与Tc-99 m即时试剂盒的开发类比，其通过将Tc-99 m高锝酸盐简单地添加到预制的、可商购的非放射性试剂盒中而获得一系列Tc-99 m放射性示踪剂，F-18即时试剂盒将不仅对制备FDG具有相同的效果，而且对制备一系列重要的分子成像探针具有相同的效果，而没有当今要求的费用和复杂性。这将使用专有的氟技术来实现。氟化学在过去十年中迅速发展，成为一种新的通用分离方法，应用范围很广。该分离是基于有机相或水相中高度氟化化合物的疏溶剂性。因此，氟相代表正交的第三相，其性质可用于简化分离和纯化。这些氟标签基本上是化学惰性的，因此提供了一种分离和纯化化合物的方法，而基本上不改变标记分子的反应性。将研究使用甘露糖三氟甲磺酸酯的氟衍生物的两种合成方法作为用于生产FDG的一步/两步工艺。将使用Am Chem Soc和DSP标准进行与本FDG制剂的纯度和鉴别的生物可比性，并将构建原型即时试剂盒。这项工作的成功完成将降低设施（热室、复杂的合成箱）的成本，并提高灵活性，以简单的一次性“即时工具包”生产许多F-18化合物。最重要的是，它将导致一系列F-18分子成像探针的广泛使用。

DESCRIPTION (provided by applicant): Since the development of the high yield nucleophilic fluorination reaction by Hamacher et al. and the development of commercially available precursors for one or two step synthesis of F-18 labeled targeted molecules, a large number of molecular imaging probes have been developed. The radiotracer having the greatest impact on clinical care is F-18 2-fluoro-2-deoxyglucose (FDG). However, the present synthesis of FDG and other F-18 labeled probes requires a hot cell (or a mini-cell) and a sophisticated multi-valve synthesis system. The final step in making F-18 radiopharmaceuticals readily available is the development of a "kit" that can produce the F-18 radiopharmaceuticals by the simple addition of F-18 fluoride to a vial with, at most, a single small column purification. By analogy with the development of the Tc-99m Instant Kits, which made a series of Tc-99m radiotracers available with the simple addition of Tc-99m pertechnetate to a pre-made, commercially available non-radioactive kit, a F-18 Instant Kit would have the same effect on making not only FDG, but a series of important molecular imaging probes available without the expense and complications of the present day requirements. This will be accomplished using proprietary fluorous technology. Fluorous chemistry has evolved rapidly over the last decade to become a new general separation method used across a wide spectrum of applications. The separation is based on the solvophobicity of highly fluorinated compounds in either organic or aqueous phases. The fluorous phase therefore represents an orthogonal third phase whose properties can be exploited to simplify separation and purification. These fluorous tags are essentially chemically inert, therefore providing a handle by which to isolate and purify compounds without substantially changing the reactivity of the tagged molecule. Two synthetic approaches using fluorous derivatives of mannose triflate will be investigated as a one/two step process for producing FDG. Biocomparability with the present FDG formulation using Am Chem Soc and DSP criteria for purity and identity will be carried out and a prototype instant kit will be constructed. The successful completion of the work will lead to reduced cost for facilities (hot cells, complicated synthesis boxes) and increased flexibility to produce many F-18 compounds with a simple, one-time use "instant kit". Most importantly, it will lead to the wide-spread use of a series of F-18 molecular imaging probes.