Bisphosphonate-functionalized gold nanoparticles for contrast-enhanced X-ray detection of breast microcalcifications

Lisa E. Cole, Tracy Vargo-Gogola, Ryan K. Roeder

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Microcalcifications are one of the most common abnormalities detected by mammography for the diagnosis of breast cancer. However, the detection of microcalcifications and correct diagnosis of breast cancer are limited by the sensitivity and specificity of mammography. Therefore, the objective of this study was to investigate the potential of bisphosphonate-functionalized gold nanoparticles (BP-Au NPs) for contrast-enhanced radiographic detection of breast microcalcifications using two models of breast microcalcifications, which allowed for precise control over levels of hydroxyapatite (HA) mineral within a low attenuating matrix. First, an invitro imaging phantom was prepared with varying concentrations of HA uniformly dispersed in an agarose hydrogel. The X-ray attenuation of HA-agarose compositions labeled by BP-Au NPs was increased by up to 26 HU compared to unlabeled compositions for HA concentrations ranging from 1 to 10mg/mL. Second, an exvivo tissue model was developed to more closely mimic the heterogeneity of breast tissue by injecting varying concentrations of HA in a Matrigel carrier into murine mammary glands. The X-ray attenuation of HA-Matrigel compositions labeled by BP-Au NPs was increased by up to 289 HU compared to unlabeled compositions for HA concentrations ranging from 0.5 to 25mg/mL, which included an HA concentration (0.5mg/mL) that was otherwise undetectable by micro-computed tomography. Cumulatively, both models demonstrated the ability of BP-Au NPs to enhance contrast for radiographic detection of microcalcifications, including at a clinically-relevant imaging resolution. Therefore, BP-Au NPs may have potential to improve clinical detection of breast microcalcifications by mammography.

Original languageEnglish (US)
Pages (from-to)2312-2321
Number of pages10
JournalBiomaterials
Volume35
Issue number7
DOIs
StatePublished - Feb 1 2014

Keywords

  • Breast cancer
  • Computed tomography
  • Contrast agent
  • Gold nanoparticles
  • Mammary gland
  • Microcalcification

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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