A gallium fluoride-18 complex containing a pentadentate macrocyclic ligand with a dimethylaminostilbene functional group designed for diagnostic imaging of Alzheimer's disease
- Author(s)
- Koay, H; Haskali, MB; Van Zuylekom, J; Cullinane, C; McLean, CA; White, JM; Roselt, PD; Donnelly, PS;
- Details
- Publication Year 2025-06-03,Volume 54,Issue #22,Page 8945-8955
- Journal Title
- Dalton Transactions
- Publication Type
- Research article
- Abstract
- 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 (H(2)L(1)) 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 Ga(III)-[(18)F]F(-) coordinate bond to give a complex, [(18)F][GaL(1)F]. This ligand can also be radiolabelled with gallium-68 to give [(68)Ga][GaL(1)F], or copper-64 to give [(64)Cu][CuL(1)]. The in vivo biodistribution of [(18)F][GaL(1)F] and [(64)Cu][CuL(1)] was evaluated in mice, revealing that the initial uptake of [(18)F][GaL(1)F] and [(64)Cu][CuL(1)] 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 [(18)F][GaL(1)F] is unstable in vivo.
- Publisher
- Royal S
- Keywords
- *Alzheimer Disease/diagnostic imaging; *Gallium Radioisotopes/chemistry; Animals; Positron-Emission Tomography; Ligands; Mice; *Stilbenes/chemistry; Humans; Fluorine Radioisotopes/chemistry; *Macrocyclic Compounds/chemistry; *Coordination Complexes/chemistry/chemical synthesis/pharmacokinetics; *Radiopharmaceuticals/chemistry/pharmacokinetics/chemical synthesis; Tissue Distribution; Brain/diagnostic imaging/metabolism; Amyloid beta-Peptides/metabolism
- Department(s)
- Cancer Imaging; Laboratory Research
- Publisher's Version
- https://doi.org/10.1039/d5dt00621j
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-06-02 04:28:20
Last Modified: 2025-07-31 02:10:16