Darpan N Pandya1, Jung Young Kim2, Wonjung Kwak1, Jeong Chan Park1, Manoj B Gawande1, Gwang Il An2, Eun Kyoung Ryu3, Jeongsoo Yoo1. 1. Department of Molecular/Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, 700-422 Republic of Korea. 2. Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea. 3. Korea Basic Science Institute, Chungbuk, 363-883 Republic of Korea.
Abstract
PURPOSE: 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. CONCLUSION: TE2A can be used by itself as a bifunctional chelator without any further structural modification.
PURPOSE: 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. CONCLUSION:TE2A can be used by itself as a bifunctional chelator without any further structural modification.
Authors: C Sissi; P Rossi; F Felluga; F Formaggio; M Palumbo; P Tecilla; C Toniolo; P Scrimin Journal: J Am Chem Soc Date: 2001-04-04 Impact factor: 15.419
Authors: Jennifer E Sprague; Yijie Peng; Xiankai Sun; Gary R Weisman; Edward H Wong; Samuel Achilefu; Carolyn J Anderson Journal: Clin Cancer Res Date: 2004-12-15 Impact factor: 12.531
Authors: Sergey Shuvaev; Elizaveta A Suturina; Nicholas J Rotile; Andrei Astashkin; Christopher J Ziegler; Alana W Ross; Tia L Walker; Peter Caravan; Ian S Taschner Journal: Dalton Trans Date: 2020-10-20 Impact factor: 4.390