title: Synthesis, characterization and in vivo studies of Cu(II)-64-labeled cross-bridged tetraazamacrocycle-amide complexes as models of peptide conjugate imaging agents.
abstract: Copper-64, a positron emitter suitable for positron emission tomography (PET), demonstrates improved in vivo clearance when chelated by the cross-bridged tetraazamacrocycle CB-TE2A compared to TETA. Good in vivo clearance was also observed for 64Cu-CB-TE2A conjugated to a peptide, which converts one coordinating carboxylate pendant arm to an amide. To better understand the in vivo stability of peptide- conjugated CB-TE2A, cross-bridged monoamides were synthesized. Crystal structures of natCu(II)-CB-TEAMA and natCu(II)-CB-PhTEAMA revealed hexadentate, distorted octahedral coordination geometry. In vivo biodistribution showed clearance of all 64Cu-radiolabeled cross-bridged monoamides from liver and bone marrow such that uptake at 24 h was <10% of uptake at 30 min. In contrast, >60% of 30 min uptake from 64Cu-TETA was retained in these tissues at 24 h. Clearance of 64Cu-cross-bridged monoamides from nontarget organs suggests good in vivo stability, thus supporting the use of CB-TE2A as a bifunctional chelator without modifications to the macrocycle backbone.
authors: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors: Jennifer E
authors: JE
authors: Sprague
authors: Yijie
authors: Y
authors: Peng
authors: Ashley L
authors: AL
authors: Fiamengo
authors: Katrina S
authors: KS
authors: Woodin
authors: Evan A
authors: EA
authors: Southwick
authors: Gary R
authors: GR
authors: Weisman
authors: Edward H
authors: EH
authors: Wong
authors: James A
authors: JA
authors: Golen
authors: Arnold L
authors: AL
authors: Rheingold
authors: Carolyn J
authors: CJ
authors: Anderson
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003301:Copper Radioisotopes; D047248:Crown Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D018360:Crystallography, X-Ray; D008024:Ligands; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
chemical_list: D000577:Amides; D002614:Chelating Agents; D003301:Copper Radioisotopes; D047248:Crown Compounds; D008024:Ligands; D019275:Radiopharmaceuticals