Contrast-enhanced X-ray detection of breast microcalcifications in a murine model using targeted gold nanoparticles

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

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Microcalcifications are deposits of hydroxyapatite (HA) mineral within breast tissue and the most common abnormality detected by mammography when screening for breast cancer due to exhibiting greater X-ray attenuation than the surrounding tissue. However, the detection of microcalcifications is limited by the sensitivity and specificity of mammography. Therefore, the objective of this study was to investigate in vivo targeted delivery of bisphosphonate- functionalized gold nanoparticles (BP-Au NPs) for contrast-enhanced detection of microcalcifications using computed tomography (CT). A murine model was developed for precise, a priori control over the level of microcalcification burden by injecting varying concentrations of HA crystals in a Matrigel carrier into mammary glands. The measured X-ray attenuation of microcalcifications containing varying HA concentrations demonstrated that the model was reproducible and able to recapitulate varying levels of microcalcification burden, including levels undetectable by CT in the absence of contrast enhancement. After intramammary delivery, BP-Au NPs provided enhanced contrast for the detection of microcalcifications that were otherwise below the CT detection limit. BP-Au NPs targeted microcalcifications due to specific binding to HA crystal surfaces, resulting in contrast between the HA microcalcification site and surrounding tissue which was visibly apparent (∼30-135 HU) within 2 days after delivery. Therefore, targeted BP-Au NPs enabled improved sensitivity and specificity for the detection of microcalcifications.

Original languageEnglish (US)
Pages (from-to)7486-7496
Number of pages11
JournalACS Nano
Volume8
Issue number7
DOIs
StatePublished - Jul 22 2014

Keywords

  • X-ray imaging
  • breast cancer
  • computed tomography
  • contrast agent
  • gold nanoparticles
  • microcalcification
  • targeted delivery

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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