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

描述（由申请人提供）：自从Hamacher等人开发出高产率的亲核氟化反应，以及开发出可用于一步或两步合成F-18标记目标分子的商业化前体以来，大量的分子成像探针被开发出来。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一个热池（或迷你池）和一个复杂的多阀合成系统。使F-18放射性药物易于获得的最后一步是开发一种“试剂盒”，该试剂盒可以生产F-18放射性药物，只需将F-18氟化物简单地添加到小瓶中，最多只需要一个小柱纯化。通过与Tc-99m即时套件的开发相类似，该套件通过简单地将Tc-99m高技术酸盐添加到预制的、市售的非放射性套件中，制作了一系列Tc-99m放射性示踪剂，F-18即时套件不仅对FDG具有相同的效果，而且还具有一系列重要的分子成像探针，无需当前要求的费用和并发症。这将使用专有的含氟技术来完成。氟化学在过去十年中发展迅速，成为一种新的通用分离方法，用于广泛的应用。分离是基于高氟化合物在有机相或水相中的疏溶剂性。因此，含氟相是一种正交的第三相，其性质可用于简化分离和纯化。这些含氟标签基本上是化学惰性的，因此提供了一个手柄，通过它可以分离和纯化化合物，而不会实质性地改变标记分子的反应性。本文将研究利用甘露糖三酸酯含氟衍生物的两种合成方法，以一/两步法生产FDG。将使用Am Chem Soc和DSP标准进行纯度和鉴定，并将构建原型即时试剂盒，与目前的FDG配方进行生物可比性。这项工作的成功完成将降低设备（热电池、复杂的合成箱）的成本，并增加灵活性，用一个简单的、一次性使用的“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.