Facile Synthesis of a Bis‐ α ‐aryl‐Substituted Pyclen‐Based Heptadentate Lanthanide Chelator for Ultra‐Robust and High‐Contrast MRI Agents and for Radiopharmaceuticals
ABSTRACT Owing to safety concerns associated with previous gadolinium‐based magnetic resonance imaging (MRI) agents, pyclen‐based Gd chelates are emerging as promising alternatives. However, the development of pyclen‐based chelators has been hindered by synthetic challenges. In this work, we report two new pyclen‐based chelators featuring α ‐aryl‐substituents on two of the acetate arms. Using the Petasis reaction, two lanthanide chelators 3a and 3b were synthesized in just two steps from pyclen. 3a‐Gd exhibits superior coordination stability and relaxivity compared to previously reported Gd 3+ chelates of comparable molecular weight. It also has low cytotoxicity and produces a strong, long‐lasting in vivo MRI signal, enabling real‐time monitoring of tissues/organs, as demonstrated in heart, liver, and kidney imaging of mice. Additionally, the chelator also shows improved coordination kinetics for In 3+ , Tb 3+ , Lu 3+ , and Y 3+ , highlighting its potential for the development of a new class of next‐generation radiopharmaceuticals.
Authors
- Nicholas J. Long (ORCID: https://orcid.org/0000-0002-8298-938X)
- Yue Wu (ORCID: https://orcid.org/0000-0001-7296-8182)
- Jean‐Claude G. Bünzli (ORCID: https://orcid.org/0000-0003-0140-3402)
- Ga‐Lai Law (ORCID: https://orcid.org/0000-0002-2192-6887)
- Edward R. H. Walter (ORCID: https://orcid.org/0000-0002-1396-3928)
- Ka‐Leung Wong (ORCID: https://orcid.org/0000-0002-3750-5980)
- Pak‐Lun Lam (ORCID: https://orcid.org/0000-0002-3558-7855)
- Ju Jiao (ORCID: https://orcid.org/0000-0003-1357-2537)
- Hei‐Yui Kai (ORCID: https://orcid.org/0000-0001-9960-7467)
- Wanqi Zhou (ORCID: https://orcid.org/0000-0002-6206-4435)
- Yik‐Hoi Yeung (ORCID: https://orcid.org/0000-0001-8446-4694)
- Stuart J. Elliott (ORCID: https://orcid.org/0000-0002-8726-0635)
- Hoa K. Chau (ORCID: https://orcid.org/0000-0001-6964-1840)
- Yujie Xie (ORCID: https://orcid.org/0009-0002-8662-7906)
- Zhengxiao Liu
- Feilong Liu
Institutions
- Hong Kong Baptist University (HK)
- Hong Kong Polytechnic University (HK)
- City University of Hong Kong (HK)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Imperial College London (GB)
- École Polytechnique Fédérale de Lausanne (CH)
Publication Details
- Journal
- Angewandte Chemie
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1002/ange.6507556
- Primary Topic
- Lanthanide and Transition Metal Complexes
- Type
- article
- Field-Weighted Citation Impact
- 0.00