title: A New Synthesis of TE2A-a Potential Bifunctional Chelator for (64)Cu.
abstract: OBJECTIVE
  The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator.
  
  
  METHODS
  TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with (64)Cu and microPET imaging was performed to follow the clearance pattern of the (64)Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with (64)Cu.
  
  
  RESULTS
  TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that (64)Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with (64)Cu in 94% yield within 30 min.
  
  
  CONCLUSIONS
  TE2A can be used by itself as a bifunctional chelator without any further structural modification.
authors.affiliation: Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea.
authors.forename: Darpan N
authors.initials: DN
authors.lastname: Pandya
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea.
authors.forename: Wonjung
authors.initials: W
authors.lastname: Kwak
authors.affiliation: Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea.
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Park
authors.affiliation: Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea.
authors.forename: Manoj B
authors.initials: MB
authors.lastname: Gawande
authors.affiliation: Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.affiliation: Korea Basic Science Institute, Chungbuk, 363-883 Republic of Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Ryu
authors.affiliation: Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea.
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
keywords: 64Cu; Bifunctional chelator; Conjugation; RGD peptide; TE2A