A novel side-bridged hybrid phosphonate/acetate pendant cyclam: synthesis, characterization, and 64Cu small animal PET imaging.
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.
Boswell
C Andrew
CA
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.
Regino
Celeste A S
CA
Baidoo
Kwamena E
KE
Wong
Karen J
KJ
Milenic
Diane E
DE
Kelley
James A
JA
Lai
Christopher C
CC
Brechbiel
Martin W
MW
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
D000085:Acetates; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D008024:Ligands; D063065:Organophosphonates; C024560:cyclam