Elemental Fluorine-18 Gas: Enhanced Production and Availability

VanBrocklin, Henry F.¹ 

[1] Department of Radiology and Biomedical Imaging

关键词: fluorine-18;    radiochemstry;    [18F]fluoromethane;    [18F]fluorine gas;    nucleophilic;    solvent exchange fluorination;   

DOI  :  10.2172/1079816
RP-ID  :  DOE/ER/64699-1
PID  :  OSTI ID: 1079816

美国|英语

来源: SciTech Connect

【 摘 要 】

The overall objective of this project was to develop an efficient, reproducible and reliable process for the preparation of fluorine-18 labeled fluorine gas ([?????F]F???) from readily available cyclotron-produced [?????F]fluoride ion. The two step process entailed the production of [?????F]fluoromethane with subsequent conversion to [?????F]F??? by electric discharge of [?????F]fluoromethane in the presence of carrier nonradioactive F??? gas. The specific goals of this project were i) to optimize the preparation of [?????F]fluoromethane from [?????F]fluoride ion; ii) to develop a prototype automated system for the production of [?????F]F??? from [?????F]fluoride ion and iii) develop a compact user friendly automated system for the preparation of [?????F]F??? with initial synthesis of fluorine-18 labeled radiotracers. Over the last decade there has been an increased interest in the production of "non-standard" positron-emitting isotopes for the preparation of new radiotracers for a variety of applications including medical imaging and therapy. The increased availability of these isotopes from small biomedical cyclotrons has prompted their use in labeling radiotracers. In much the same way the production of [?????F]F??? gas has been known for several decades. However, access to [?????F]F??? gas has been limited to those laboratories with the means (e.g. F??? targetry for the cyclotron) and the project-based need to work with [?????F]F??? gas. Relatively few laboratories, compared to those that produce [?????F]fluoride ion on a daily basis, possess the capability to produce and use [?????F]F??? gas. A simplified, reliable system employing [?????F]fluoride ion from cyclotron targetry systems that are already in place coupled with on-demand production of the [?????F]F??? gas would greatly enhance its availability. This would improve the availability of [?????F]F??? gas and promote further work with a valuable precursor. The major goals of the project were accomplished over the funding period. The preparation of ?????F]fluoromethane has been automated with reproducible yields greater than 90% conversion from [?????F]fluoride ion. A trap and release system was established for the [?????F]fluoride ion concentration and direct elution of the [?????F]fluoride ion into the reaction vial with the appropriate base and precursor in DMSO. Other solvents were also investigated. The production time for [?????F]fluoromethane is less than 10 minutes. An automated system for the [?????F]F??? gas production from the [18F]fluoromethane has been developed. The unit coupled to the [?????F]fluoromethane system permits the on demand production of [?????F]F??? gas. In less than 30 minutes, mCi quantities of [?????F]F??? gas were produced. Several variables for the [?????F]F??? gas production were investigated and a set of parameters for reproducible operation were determined. These parameters included discharge chamber size, carrier gas (He, Ne, Ar), discharge time, discharge current, mass of F??? gas added to the chamber. FDOPA and EF5 were used to test the reactivity of the [?????F]F??? gas. Both products were produced in low to modest yield. The ready availability of [?????F]F??? gas has potential impact to advance both DOE mission-driven initiatives and nuclear medicine initiatives through other federally funded agencies such as NIH and DoD. New reactions involving the use of [?????F]F??? gas will lead to direct labeling of new radiotracers and intermediates as well as new fluorine-18 labeled synthons that may be further reacted with other reagents to provide useful fluorine-18 labeled compounds. New tracers to understand and follow plant and microbial metabolism as well as new tracers for nuclear medicine applications, that have been either difficult to obtain or never produced due to the limited availability of [?????F]F??? gas, may be prepared using the techniques developed .