[18F]D3FSP ([18F]D3AV-45) as a PET imaging agent for Abeta plaques in the brain.

1031 Objectives: Replacement of the carbon hydrogen bond (C-H) with a carbon-deuterium (C-D) bond often increases in vivo metabolic stability through a reduction in drug metabolism. FDA has recently approved a new deuterated drug, deuterated tetrabenazine (SD-809, Austedo) for treatment of Huntington’s disease. Amyvid (florbetapir, [18F]AV-45) is currently a commercially available PET imaging agent targeting Aβ plaques in the brain for assisting the diagnosis of Alzheimer’s disease. A deuterated analog, [18F]D3FSP ([18F]D3AV-45), was prepared and tested for mapping Aβ plaques in the brain. Methods: [18F]D3FSP, a potential PET imaging agent targeting amyloid plaques in the brain, was prepared using a reaction sequence similar to that of [18F]AV-45. [18F]D3FSP was tested by in vitro binding, autoradiography and in vivo biodistribution studies in normal mice. Results: Binding studies, using either [18F]D3FSP or [18F]AV-45 as the hot ligand, showed that hydrogen to deuterium substitution (AV-45 vs D3FSP) showed the same excellent binding affinity to Aβ aggregate binding sites (Ki = 3 to 4 nM). Within statistical errors the biodistribution of [18F]-AV-45 and [18F]D3FSP in normal mice showed very similar results. [18F]D3FSP and [18F]AV-45 showed comparable initial brain penetration at 2 min after an iv injection with rapid washout in the normal mice brain as shown at later time points (60 and 120 min). Autoradiography of AD brain sections using these two ligands showed very similar binding pattern confirming the high binding affinity to Aβ aggregates. Conclusion: The preliminary results suggest that [18F]D3FSP is a potential PET imaging agent for mapping Aβ plaques in the brain.