Ground Fluor Technology

Ground Fluor Pharmaceuticals, Inc., (GFP) is the exclusive worldwide licensee to a breakthrough iodonium chemistry for the rapid, carrier-free, high-yielding synthesis of F18-Positron Emission Tomography (PET) imaging agents.  SWIFT™ technology allows Swift Fluorine Tagging of small molecules.  The technology was developed by Dr. Stephen DiMagno at the University of Nebraska- Lincoln.  Technology licensees can now rapidly produce finished, highly potent (no-carrier-added) pharmaceutical F18 PET agents in very high yields using conventional modular synthesizers available in the industry.  No heavy metals are used in the synthetic processes, and purification of final product can generally be performed using single phase extraction (SPE) without the need for high pressure liquid chromatography (HPLC).

Aryl fluorides are structural moieties in natural products as well as a number of therapeutically important compounds, including positron emission tomography (PET) tracers and pharmaceuticals.  Ground Fluor Pharmaceuticals has developed novel methods of preparing substituted aryl and heteroaryl ring systems using diaryliodonium compounds and intermediates.  For example, diaryliodonium salts and diaryliodonium fluorides, as developed by the Company, can undergo decomposition to prepare an aryl fluoride.

For example, 6-[18F]-Fluorodopamine (6-[18F]FDA) has been shown to be a promising imaging biomarker of neuroblastoma and of pheochromocytoma.  6-[18F]-L-DOPA has been shown to be a promising biomarker in patients with Parkinson’s disease.  However, the availability of these agents for research and clinical studies is limited by the duration, complexity, low radiochemical yields (RCY) of available synthetic processes, low specific activity of the final product and the lack of reproducibility of existing synthetic techniques.  Currently, the low specific activity synthesis (10 Ci/mmol) of the final [18F]FDA product also limits its use.  A no-carrier-added synthesis of 6-[18F]FDA has been demonstrated elsewhere9 with high specific activity (2-5 Ci/µmol); however, the process gives low RCY, making routine automated production difficult. Here, we report a one-pot, two-step synthesis of 6-[18F]FDA and of 6-[18F]-L-DOPA, each with high specific activity and high radiochemical yield with a total synthesis time of 45 minutes EOB.

Working with collaborators at St. Jude Children’s Research Center, reductive elimination of diaryliodonium salts in nonpolar solvents was confirmed to dramatically increase 18F incorporation.  Reactions performed in acetonitrile yielded little to no (1-2%) product for [18F]FDA and [18F]-L-DOPA, while thermal decomposition in toluene gave 68 ± 3% and 38 ±5% of [18F]FDA and [18F]-L-DOPA, respectively.

There is a broadly acknowledged need for biomarkers which can provide specific information about physiologic function, about pathophysiology and about response to clinical interventions on a patient by patient basis.  Translational medicine, the effort to transition basic research discoveries into clinical applications which benefit patients, requires the support of technologies which allow rapid assessment of the relevance and benefit of new interventions in individuals.  The patented single step, no carrier added synthesis of 18F-labeled PET agents, which is the basis of GFP’s activities, is intended to support pharmaceutical development of new effective therapeutic agents by providing a tool for the rapid assessment of in vivo biodistribution and drug targeting.

GFP provides licenses and research and development assistance to third-parties seeking to prepare F-18 radiolabeled proprietary products. In addition, GFP is developing its own PET agents using its proprietary technology.

For further information, please contact Dr. Stephen DiMagno at 402-875-0055 |  stephendimagno@gfpharma.com or Dr. Allan Green at 617-447-5999 | amgreen@gfpharma.com.