title: Gold Nanoclusters Doped with (64)Cu for CXCR4 Positron Emission Tomography Imaging of Breast Cancer and Metastasis.
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 (64)Cu doped gold nanocluster ((64)CuAuNC, 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 (64)CuAuNCs-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 (64)CuAuNCs-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 (64)CuAuNCs and (64)Cu-AMD3100 alone, the targeted (64)CuAuNCs-AMD3100 detected up-regulated CXCR4 in early stage tumors and premetastatic niche of lung earlier and with greater sensitivity. Taken together, we believe that (64)CuAuNCs-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.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Detering
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Deborah
authors.initials: D
authors.lastname: Sultan
authors.affiliation: Department of Medicine, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Cooper
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Meng
authors.initials: M
authors.lastname: You
authors.affiliation: Department of Chemistry, Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77842, United States.
authors.forename: Sangho
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Medicine, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Meier
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Hannah
authors.initials: H
authors.lastname: Luehmann
authors.affiliation: Department of Chemistry, Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77842, United States.
authors.forename: Guorong
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Medicine, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Rettig
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.affiliation: Department of Chemistry, Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77842, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley
authors.affiliation: Department of Medicine, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University , St. Louis, Missouri 63110, United States.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D049329:Nanostructures; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019718:Receptors, CXCR4
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D006046:Gold
keywords: CXCR4; breast cancer; lung metastasis; nanocluster; positron emission tomography