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

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.