Synlett 2019; 30(15): 1795-1798
DOI: 10.1055/s-0039-1690194
letter
© Georg Thieme Verlag Stuttgart · New York

A Multifunctional HBED-Type Chelator with Dual Conjugation Capabilities for Radiopharmaceutical Development

Ata Makarem
a   German Cancer Research Center (DKFZ) Heidelberg, Division of Radiopharmaceutical Chemistry, INF 223, d-69120 Heidelberg, Germany   Email: a.makarem@dkfz.de
b   The Institute of Cancer Research, Division of Radiotherapy and Imaging, 123 Old Brompton Road, SW7 3RP, London, UK
,
Mohammadreza Kamali Sarvestani
a   German Cancer Research Center (DKFZ) Heidelberg, Division of Radiopharmaceutical Chemistry, INF 223, d-69120 Heidelberg, Germany   Email: a.makarem@dkfz.de
c   Ruprecht-Karls-Universität-Heidelberg, Institute of Inorganic Chemistry, INF 270, DE-69120 Heidelberg, Germany
,
Karel D. Klika
d   German Cancer Research Center (DKFZ) Heidelberg, Molecular Structure Analysis, INF 280, d-69120 Heidelberg, Germany
,
Klaus Kopka
a   German Cancer Research Center (DKFZ) Heidelberg, Division of Radiopharmaceutical Chemistry, INF 223, d-69120 Heidelberg, Germany   Email: a.makarem@dkfz.de
e   German Cancer Consortium (DKTK), d-69120 Heidelberg, Germany
› Author Affiliations
This work was partly funded by a grant from German Cancer Aid (Deutsche Krebshilfe), project number 70112043.
Further Information

Publication History

Received: 22 July 2019

Accepted after revision: 15 August 2019

Publication Date:
26 August 2019 (online)


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Abstract

Bifunctional HBED chelators are hexadentate complexing ligands (chelators) that tightly coordinate to trivalent gallium and, additionally, are able to bind to bioactive molecules. In nuclear medicine, HBED-based radiopharmaceuticals are used as powerful radiotracers for tumor imaging. Among variants of bifunctional HBED chelators, HBED-CC is the most well-known; it possesses two terminal carboxylic acid groups that are able to undergo bioconjugation by amide-bond formation. However, to permit bioconjugation through click coupling, we previously modified the structure of HBED-CC and introduced HBED-NN chelator bearing two azide functions. We have now combined the conjugation capabilities of HBED-CC and HBED-NN chelators in one molecule and have created HBED-NC, which possesses both azide and carboxylic acid groups. The advantage of HBED-NC is that it provides options for constructing either monomeric or heterodimeric radiolabeling precursors. This work describes the synthesis of HBED-NC by either of two pathways.

Supporting Information