title: A novel side-bridged hybrid phosphonate/acetate pendant cyclam: synthesis, characterization, and 64Cu small animal PET imaging.
abstract: Copper-64 (t(1/2)=12.7h; beta(+): 0.653 MeV, 17.4%; beta(-): 0.578 MeV, 39%) is produced in a biomedical cyclotron and has applications in both imaging and therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind copper radionuclides to antibodies and peptides owing to their relatively high kinetic stability. A novel side-bridged cyclam featuring both pendant acetate and phosphonate groups was synthesized using a Kabachnik-Fields approach followed by hydrobromic acid deprotection. The Cu(II) complex of the novel ligand was synthesized, radiolabeling with (64)Cu was demonstrated, and in vitro (serum) stability was performed. In addition, in vivo distribution and clearance of the (64)Cu-labeled complex was visualized by positron emission tomography (PET) imaging. This novel chelate may be useful in (64)Cu-mediated diagnostic positron emission tomography (PET) imaging as well as targeted radiotherapeutic applications.
authors.affiliation: Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10 Center Drive, Bethesda, MA 20892-1088, United States.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Boswell
authors.forename: Celeste A S
authors.initials: CA
authors.lastname: Regino
authors.forename: Kwamena E
authors.initials: KE
authors.lastname: Baidoo
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Wong
authors.forename: Diane E
authors.initials: DE
authors.lastname: Milenic
authors.forename: James A
authors.initials: JA
authors.lastname: Kelley
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Lai
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
mesh_terms: D000085:Acetates; D000818:Animals; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008024:Ligands; D051379:Mice; D063065:Organophosphonates; D049268:Positron-Emission Tomography; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D008024:Ligands; D063065:Organophosphonates; C024560:cyclam