Nucleophilic Fluorination Reactions in Novel Reaction Media for 18F-Fluorine Labeling Method / 핵의학분자영상

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography (PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with 18F-fluorine. In this review we describe recent methods and novel trends for the introduction of 18F-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic 18F-fluorination of some halo- and mesyloxyalkanes to the corresponding 18F-fluoroalkanes with 18F-fluoride obtained from an 18O(p,n)18F reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for 18F-fluorine labeling. Ionic liquid method is rapid and particularly convenient because 18F-fluoride in H2O can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with 18F-fluorine for PETimaging, and it is illustrated by the synthesis of 18F-fluoride radiolabeled molecular imaging probes, such as 18F-FDG, 18F-FLT, 18F-FP-CIT, and 18F-FMISO, in high yield and purity and in shorter times compared to conventional syntheses

Production of 18FF2 Gas for Electrophilic Substitution Reaction / 핵의학분자영상

PURPOSE: Electrophilic 18F (T1/2=110 min) radionuclide in the form of [18F]F2 gas is of great significance for labeling radiopharmaceuticals for positron emission tomography (PET). However, its production in high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of [18F]F2 for the electrophilic substitution reaction. MATERIALS AND METHODS: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the 18O(p,n)18F reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched 18O2 was irradiated with protons for 18F production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas (1% [19F]F2/Ar) was loaded into the target chamber, following a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and 18O2 loading pressure. RESULTS: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97 % enriched 18O2, 13.2 MeV protons, 30 micro A, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% [19F]fluorine/argon gas, 13.2 MeV protons, 30 micro A, 20-30 min irradiation), the recovery of [18F]fluorine for synthesis. The yield of [18F]fluorine at EOB (end of bombardment) was achieved around 34+/-6.0 GBq (n>10). CONCLUSION: The production of 18F electrophilic agent via 18O(p,n)18F reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of [18F]fluorine. These results suggest the possibility to use [18F]F2 gas as a electrophilic substitution agent.