Gold Nanoclusters Doped with 64Cu for CXCR4 Positron Emission Tomography Imaging of Breast Cancer and Metastasis

Yongfeng Zhao, Lisa Detering, Deborah Sultan, Matthew L. Cooper, Meng You, Sangho Cho, Stephanie L. Meier, Hannah Luehmann, Guorong Sun, Michael Rettig, Farrokh Dehdashti, Karen L. Wooley, John F. DiPersio, Yongjian Liu

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

As an emerging class of nanomaterial, nanoclusters hold great potential for biomedical applications due to their unique sizes and related properties. Herein, we prepared a 64Cu doped gold nanocluster (64CuAuNC, hydrodynamic size: 4.2 ± 0.5 nm) functionalized with AMD3100 (or Plerixafor) for targeted positron emission tomography (PET) imaging of CXCR4, an up-regulated receptor on primary tumor and lung metastasis in a mouse 4T1 orthotopic breast cancer model. The preparation of targeted 64CuAuNCs-AMD3100 (4.5 ± 0.4 nm) was done via one-step reaction with controlled conjugation of AMD3100 and specific activity, as well as improved colloid stability. In vivo pharmacokinetic evaluation showed favorable organ distribution and significant renal and fecal clearance within 48 h post injection. The expression of CXCR4 in tumors and metastasis was characterized by immunohistochemistry, Western blot, and reverse transcription polymerase chain reaction analysis. PET imaging with 64CuAuNCs-AMD3100 demonstrated sensitive and accurate detection of CXCR4 in engineered tumors expressing various levels of the receptor, while competitive receptor blocking studies confirmed targeting specificity of the nanoclusters. In contrast to nontargeted 64CuAuNCs and 64Cu-AMD3100 alone, the targeted 64CuAuNCs-AMD3100 detected up-regulated CXCR4 in early stage tumors and premetastatic niche of lung earlier and with greater sensitivity. Taken together, we believe that 64CuAuNCs-AMD3100 could serve as a useful platform for early and accurate detection of breast cancer and metastasis providing an essential tool to guide the treatment.

Original languageEnglish
Pages (from-to)5959-5970
Number of pages12
JournalACS nano
Volume10
Issue number6
DOIs
StatePublished - Jun 28 2016

Keywords

  • CXCR4
  • breast cancer
  • lung metastasis
  • nanocluster
  • positron emission tomography

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