Adapting the C-11 methylation module for [F-18]-PET Radiopharmaceuticals

To make multi-functional use of the C-11 methylation module and adapt it for nucleophilic fluorination studies.

[C-11]-labeled PET Radiopharmaceuticals (RPs) have provided a lot of physiologic and metabolic information in several diseases. However, due to its very short half-life (T½ = 20 min), and the significant auto-radiolytic damage of molecules labeled with it, it has largely remained as a R & D tool. [C-11]-labeled RPs are routinely used in only a few PET-centres and the emphasis is to substitute them with [F-18]-labeled equivalents. Our [C-11]-methylation module uses the reduction of cyclotron produced [C-11]-CO₂ to [C-11]-methyl iodide which is then used for methylation. This method is cumbersome with poor yields and the cleaning process is lengthy. The reagents are very labile, hygroscopic and not available in single use aliquots as for [F-18]-FDG, [F-18]-FLT etc. Realizing this, the present approach to [C-11]-tracers is to produce [C-11]-CH4 in the cyclotron target and convert it [C-11]-methyl iodide by heating with iodine vapours. Hence, we decided to adapt the module for nucleophilic fluorination. This was carried out by changing reconnecting the various tubings valves, and programming the NINA software for the sequence of operations for different fluorination conditions keeping in mind the dimensions of the reaction vessels, heating and cooling rates, gas flow rates, etc, etc. The process was mostly logical with some trial and error. Using reagents from ABX Advanced Biochemical Company, Germany, the synthesis of [F-18]-FDG and [F-18]-FLT were carried out. [F-18]-NaF was also produced.

We have got very satisfactory yields for [F-18]-FDG and [F-18]-FLT. The products fulfilled the requisite QC tests for biodistribution studies in animals with excellent results. With the increased number of different [F-18]-PET RPs that are likely to be used in patient management, particularly in oncology, and with the high cost of equipment and space, it is not possible to have individual synthesis modules for different [F-18]-molecules. A general purpose synthesis module is a viable solution if one schedules the production followed by a thorough cleaning after each synthesis.