64Cu/177Lu-DOTA-diZD, a Small-Molecule-Based Theranostic Pair for Triple-Negative Breast Cancer

Yuqian Huang, Zhen Yang, Feng Li, Hong Zhao, Chun Li, Nam Yu, Dale J Hamilton, Zheng Li

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Despite advances in targeted therapies, the prognosis for patients with triple-negative breast cancer (TNBC) is poor because there are few actionable molecular targets. The dependence of solid tumor growth on angiogenesis prompted our development of angiogenic-receptor-targeted radionuclide therapy (TRT) to treat TNBC by targeted delivery of therapeutic doses of ionizing radiation to tumors. A high-affinity vascular endothelial growth factor receptor (VEGFR)-targeted agent, diZD, was synthesized and labeled with 177Lu and 64Cu by 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator giving the TRT agent, 177Lu-DOTA-diZD, and PET imaging agent, 64Cu-DOTA-diZD. We showed that "64Cu/177Lu"-DOTA-diZD radiotracers are a promising theranostic pair for TNBC. 4T1-bearing mice treated with 177Lu-DOTA-diZD-based TRT survived with a median of 28 days, which was significantly longer than that of control mice as 18 days. Anti-PD1 immunotherapy resulted in a shorter median survival of 16 days. This work presents for the first time that small-molecule VEGFR-oriented TRT is a promising therapeutic option to treat "immunogenic cold" TNBC.

Original languageEnglish (US)
Pages (from-to)2705-2713
Number of pages9
JournalJournal of Medicinal Chemistry
Issue number5
StatePublished - Mar 11 2021

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine


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