Contrast-Enhanced X-ray Detection of Microcalcifications in Radiographically Dense Mammary Tissue Using Targeted Gold Nanoparticles

Breast density reduces the accuracy of mammography, motivating methods to improve sensitivity and specificity for detecting abnormalities within dense breast tissue, but preclinical animal models are lacking. Therefore, the objectives of this study were to investigate a murine model of radiographically dense mammary tissue and contrast-enhanced X-ray detection of microcalcifications in dense mammary tissue by targeted delivery of bisphosphonate-functionalized gold nanoparticles (BP-Au NPs). Mammary glands (MGs) in the mouse mammary tumor virus - polyomavirus middle T antigen (MMTV-PyMT or PyMT) model exhibited greater radiographic density with age and compared with strain- and age-matched wild-type (WT) controls at 6-10 weeks of age. The greater radiographic density of MGs in PyMT mice obscured radiographic detection of microcalcifications that were otherwise detectable in MGs of WT mice. However, BP-Au NPs provided enhanced contrast for the detection of microcalcifications in both radiographically dense (PyMT) and WT mammary tissues as measured by computed tomography after intramammary delivery. BP-Au NPs targeted microcalcifications to enhance X-ray contrast with surrounding mammary tissue, which resulted in improved sensitivity and specificity for detection in radiographically dense mammary tissues.