Indian Journal of Nuclear Medicine

Routine production of parenteral-grade [¹⁸F]-NaF as per US-FDA specifications

Enriched [¹⁸O]-water from ROTEM is irradiated by protons to produce ¹⁸F⁻ by ¹⁸O(p,n)¹⁸F nuclear reaction in a 16 MeV Medical Cyclotron at the BARC - Medical Cyclotron Facility at Parel, Mumbai. Chromafix 45-PS-HCO⁻₃, anion exchange column was from Chromafix, Germany. Pharmaceutical Grade isotonic saline was procured from ABX Advanced Biochemical Company, Germany. Sterile, pyrogen-free and evacuated vials (Pyrovac®) for dispensing the [¹⁸F]-NaF were from Acila A.G., Germany. TLC plates, HPLC Grade water and DNA-grade acetonitrile and 0.2 μm sterilization filters were locally procured.

¹⁸F⁻ produced from the cyclotron is extracted from the target ¹⁸O-water in the anion exchange column and then eluted with sterile normal saline. Dilution if required is also done with normal saline. The total time for production is about 5 minutes and it is carried out in the general purpose fluorination module and indigenously modified NINA-based software. The required amounts of the [¹⁸F]-NaF is then dispensed into vials through 0.2μm filter housed in a class 100 area and rapidly autoclaved at 134 ºC for 5 minutes. Quality control tests are done according to the pharmacopoeia guide line (clarity, pH ∼ 7, RCP: R_f of [F-18] NaF is 0.0–0.05 in 95% aqueous MeCN, RNP by half life [110±5 minutes] as well as HPGe). PET-CT fusion imaging studies were carried out in rabbits. Several patient-volunteers having different type of bone-related problems were also studied.

So far 68 trial batches of [¹⁸F]-NaF have been produced and fulfills all US-FDA specifications for the product. RPC clearance for routine supply to users is under way and will be obtained soon. PET-CT fusion scans of rabbits show excellent imaging of the whole skeletal system. PET-CT scans of volunteers having different bone related problems like osteoporotic changes, osteochondroma etc. are very satisfactory. We are happy to conclude that we are in a position for routine supply of [F-18] NaF as a PET radiopharmaceutical for skeletal imaging as well as a better probe than MDP.