title: Bisphosphonate-functionalized gold nanoparticles for contrast-enhanced X-ray detection of breast microcalcifications.
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 in vitro 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 10 mg/mL. Second, an ex vivo 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 25 mg/mL, which included an HA concentration (0.5 mg/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.
authors.affiliation: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Cole
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University Simon Cancer Center, Indiana University School of Medicine - South Bend, South Bend, IN 46617, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Vargo-Gogola
authors.affiliation: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: rroeder@nd.edu.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Roeder
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000175:diagnosis*; D003287:Contrast Media; D004164:Diphosphonates / Q000737:chemistry*; D005260:Female; D006046:Gold / Q000737:chemistry*; D008321:Mammary Glands, Animal / Q000473:pathology*; D008327:Mammography / Q000379:methods*; D053768:Metal Nanoparticles; D051379:Mice; D019047:Phantoms, Imaging
chemical_list: D003287:Contrast Media; D004164:Diphosphonates; D006046:Gold
keywords: Breast cancer; Computed tomography; Contrast agent; Gold nanoparticles; Mammary gland; Microcalcification