A Gallium Fluoride-18 Complex Containing a Pentadentate Macrocyclic Ligand with a Dimethylaminostilbene Functional Group Designed for Diagnostic Imaging of Alzheimer's Disease.

The molecular pathology of Alzheimer's disease is associated with the presence of aggregates of amyloid-β, a 39-43 amino acid peptide, that form amyloid plaques in the brain. Appropriately substituted stilbene derivatives, radiolabelled with positron-emitting radionuclides, that bind selectively to amyloid-β plaques can be used to assess plaque burden by Positron Emission Tomography (PET) imaging and assist in the diagnosis of Alzheimer's disease. In this work, a substituted pentadentate ligand based on a triazacyclononane backbone (H2L1) with one pendent stilbene functional group and two pendent carboxylate groups was synthesised. The new ligand binds to amyloid-β plaques present in human brain tissue. Non-conventional radiolabelling with fluorine-18 was achieved by the formation of a GaIII-[18F]F- coordinate bond to give a complex, [18F][GaL1F]. This ligand can also be radiolabelled with gallium-68 to give [68Ga][GaL1F], or copper-64 to give [64Cu][CuL1]. The in vivo biodistribution of [18F][GaL1F] and [64Cu][CuL1] was evaluated in mice, revealing that the initial uptake of [18F][GaL1F] and [64Cu][CuL1] in the brain was 0.85 ± 0.13% IA g-1 and 0.71 ± 0.03% IA g-1 respectively. An increase in radioactivity in bone at later time points suggested that [18F][GaL1F] is unstable in vivo.