{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:17:25Z","timestamp":1791224245110,"version":"4.1.0"},"reference-count":52,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T00:00:00Z","timestamp":1404345600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T00:00:00Z","timestamp":1404345600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T00:00:00Z","timestamp":1404345600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100001377","name":"Walther Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001377","id-type":"DOI","asserted-by":"publisher"}]},{"name":"St. Joseph Regional Medical Center, Mishawaka, IN"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 (\u223c30\u2013135 HU) within 2 days after delivery. Therefore, targeted BP-Au NPs enabled improved sensitivity and specificity for the detection of microcalcifications.<\/jats:p>","DOI":"10.1021\/nn5027802","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T19:37:09Z","timestamp":1404416229000},"page":"7486-7496","source":"Crossref","is-referenced-by-count":32,"title":["Contrast-Enhanced X\u2011ray Detection of Breast Microcalcifications in a Murine Model Using Targeted Gold Nanoparticles"],"prefix":"10.1021","volume":"8","author":[{"given":"Lisa E.","family":"Cole","sequence":"first","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]},{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Vargo-Gogola","sequence":"additional","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]},{"name":"Indiana University Simon Cancer, Center Indiana University School of Medicine , \u2212 South Bend, , ,","place":["South Bend, Indiana, United States, 46617"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan K.","family":"Roeder","sequence":"additional","affiliation":[{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]},{"name":"University of Notre Dame , , , ,","place":["Notre Dame, Indiana, United States, 46556"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,7,3]]},"reference":[{"key":"2026081809132851500_cit1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrc1041","article-title":"The Case for Early Detection","volume":"3","author":"Etzioni","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"2026081809132851500_cit2","first-page":"471","article-title":"Breast Cancer Screening: The Evolving Evidence","volume":"26","author":"Smith","year":"2012","journal-title":"Oncology"},{"key":"2026081809132851500_cit3","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nature06917","article-title":"Imaging in the Era of Molecular Oncology","volume":"452","author":"Weissleder","year":"2008","journal-title":"Nature"},{"key":"2026081809132851500_cit4","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1001\/jama.293.10.1245","article-title":"Screening for Breast Cancer","volume":"293","author":"Elmore","year":"2005","journal-title":"JAMA, J. Am. Med. Assoc."},{"key":"2026081809132851500_cit5","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0140-6736(85)92204-4","article-title":"Reduction in Mortality From Breast Cancer After Mass Screening with Mammography. Randomised Trial From the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare","volume":"325","author":"Taba\u0301r","year":"1985","journal-title":"Lancet"},{"key":"2026081809132851500_cit6","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1148\/radiol.11110469","article-title":"Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality During Three Decades","volume":"260","author":"Taba\u0301r","year":"2011","journal-title":"Radiology"},{"key":"2026081809132851500_cit7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s10911-005-5400-6","article-title":"Microcalcifications Associated with Breast Cancer: An Epiphenomenon or Biologically Significant Feature of Selected Tumors?","volume":"10","author":"Morgan","year":"2005","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"2026081809132851500_cit8","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1016\/S0031-3203(03)00192-4","article-title":"Computer-Aided Detection and Classification of Microcalcifications in Mammograms: A Survey","volume":"36","author":"Cheng","year":"2003","journal-title":"Pattern Recogn."},{"key":"2026081809132851500_cit9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0720-048X(02)00181-X","article-title":"Evaluation of Breast Microcalcifications According to Breast Imaging Reporting and Data System Criteria and Le Gal\u2019s Classification","volume":"47","author":"Gu\u0308lsu\u0308n","year":"2003","journal-title":"Eur. J. Radiol."},{"key":"2026081809132851500_cit10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/BF00710823","article-title":"Different Types of Microcalcifications Observed in Breast Pathology","volume":"410","author":"Frappart","year":"1986","journal-title":"Virchows Arch. A: Pathol. Anat. Histol."},{"key":"2026081809132851500_cit11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF00430830","article-title":"Differences in Microcalcification in Breast Tumors","volume":"393","author":"Bu\u0308sing","year":"1981","journal-title":"Virchows Arch. A: Pathol. Anat. Histol."},{"key":"2026081809132851500_cit12","first-page":"5375","article-title":"Identifying Microcalcifications in Benign and Malignant Breast Lesions by Probing Differences in Their Chemical Composition Using Raman Spectroscopy","volume":"62","author":"Haka","year":"2002","journal-title":"Cancer Res."},{"key":"2026081809132851500_cit13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1259\/bjr\/13169882","article-title":"Gold Nanoparticles: A New X-Ray Contrast Agent","volume":"79","author":"Hainfeld","year":"2006","journal-title":"Br. J. Radiol."},{"key":"2026081809132851500_cit14","doi-asserted-by":"crossref","first-page":"7661","DOI":"10.1021\/ja071471p","article-title":"Antibiofouling Polymer-Coated Gold Nanoparticles as a Contrast Agent for In Vivo X-Ray Computed Tomography Imaging","volume":"129","author":"Kim","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2026081809132851500_cit15","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1097\/RLI.0b013e31811ecdcd","article-title":"Colloidal Gold Nanoparticles as a Blood-Pool Contrast Agent for X-Ray Computed Tomography in Mice","volume":"42","author":"Cai","year":"2007","journal-title":"Invest. Radiol."},{"key":"2026081809132851500_cit16","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1039\/b712170a","article-title":"Biological Applications of Gold Nanoparticles","volume":"37","author":"Sperling","year":"2008","journal-title":"Chem. Soc. Rev."},{"key":"2026081809132851500_cit17","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1021\/nl8029114","article-title":"Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer","volume":"8","author":"Popovtzer","year":"2008","journal-title":"Nano Lett."},{"key":"2026081809132851500_cit18","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s11307-010-0299-8","article-title":"AuNP-DG: Deoxyglucose-Labeled Gold Nanoparticles as X-Ray Computed Tomography Contrast Agents for Cancer Imaging","volume":"12","author":"Aydogan","year":"2010","journal-title":"Mol. Imaging Biol."},{"key":"2026081809132851500_cit19","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1088\/0031-9155\/55\/15\/013","article-title":"A Novel Functional CT Contrast Agent for Molecular Imaging of Cancer","volume":"55","author":"Li","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"2026081809132851500_cit20","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1021\/nn901877h","article-title":"A Drug-Loaded Aptamer-Gold Nanoparticle Bioconjugate for Combined CT Imaging and Therapy of Prostate Cancer","volume":"4","author":"Kim","year":"2010","journal-title":"ACS Nano"},{"key":"2026081809132851500_cit21","doi-asserted-by":"crossref","first-page":"8760","DOI":"10.1073\/pnas.1002143107","article-title":"Bombesin Functionalized Gold Nanoparticles Show In Vitro and In Vivo Cancer Receptor Specificity","volume":"107","author":"Chanda","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081809132851500_cit22","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1021\/nl101019s","article-title":"Anti-CD4-Targeted Gold Nanoparticles Induce Specific Contrast Enhancement of Peripheral Lymph Nodes in X-Ray Computed Tomography of Live Mice","volume":"10","author":"Eck","year":"2010","journal-title":"Nano Lett."},{"key":"2026081809132851500_cit23","first-page":"2859","article-title":"Targeted Gold Nanoparticles Enable Molecular CT Imaging of Cancer: An In Vivo Study","volume":"6","author":"Reuveni","year":"2011","journal-title":"Int. J. Nanomed."},{"key":"2026081809132851500_cit24","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1259\/bjr\/42612922","article-title":"Micro-CT Enables Microlocalisation and Quantification of Her2-Targeted Gold Nanoparticles Within Tumour Regions","volume":"84","author":"Hainfeld","year":"2011","journal-title":"Br. J. Radiol."},{"key":"2026081809132851500_cit25","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.biomaterials.2012.09.054","article-title":"Folic Acid-Modified Dendrimer-Entrapped Gold Nanoparticles as Nanoprobes for Targeted CT Imaging of Human Lung Adenocarcinoma","volume":"34","author":"Wang","year":"2013","journal-title":"Biomaterials"},{"key":"2026081809132851500_cit26","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1002\/chem.201204612","article-title":"Targeted Tumor Computed Tomography Imaging Using Low-Generation Dendrimer-Stabilized Gold Nanoparticles","volume":"19","author":"Liu","year":"2013","journal-title":"Chem.\ue5f8Eur. J."},{"key":"2026081809132851500_cit27","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.1016\/j.biomaterials.2013.03.009","article-title":"Targeted CT\/MR Dual Model Imaging of Tumors Using Multifunctional Dendrimer-Entrapped Gold Nanoparticles","volume":"34","author":"Chen","year":"2013","journal-title":"Biomaterials"},{"key":"2026081809132851500_cit28","article-title":"Biocompatible Glycol Chitosan-Coated Gold Nanoparticles for Tumor-Targeting CT Imaging","author":"Sun","year":"2013","journal-title":"Pharm. Res."},{"key":"2026081809132851500_cit29","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/j.biomaterials.2013.11.077","article-title":"Bisphosphonate-Functionalized Gold Nanoparticles for Contrast-Enhanced X-Ray Detection of Breast Microcalcifications","volume":"35","author":"Cole","year":"2014","journal-title":"Biomaterials"},{"key":"2026081809132851500_cit30","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s11051-012-1175-z","article-title":"Relative Binding Affinity of Carboxylate-, Phosphonate-, and Bisphosphonate-Functionalized Gold Nanoparticles Targeted to Damaged Bone Tissue","volume":"14","author":"Ross","year":"2012","journal-title":"J. Nanopart. Res."},{"key":"2026081809132851500_cit31","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/jbm.a.33165","article-title":"Binding Affinity of Surface Functionalized Gold Nanoparticles to Hydroxyapatite","volume":"99A","author":"Ross","year":"2011","journal-title":"J. Biomed. Mater. Res."},{"key":"2026081809132851500_cit32","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1021\/cm4035616","article-title":"Effect of Functionalized Gold Nanoparticle Size on X-Ray Attenuation and Binding Affinity to Hydroxyapatite","volume":"26","author":"Ross","year":"2014","journal-title":"Chem. Mater."},{"key":"2026081809132851500_cit33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/bjc.2011.583","article-title":"Microcalcifications in Breast Cancer: Novel Insights Into the Molecular Mechanism and Functional Consequence of Mammary Mineralisation","volume":"106","author":"Cox","year":"2012","journal-title":"Br. J. Cancer"},{"key":"2026081809132851500_cit34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2310\/7290.2008.00018A","article-title":"Humoral Bone Morphogenetic Protein-2 Is Sufficient for Inducing Breast Cancer Microcalcification","volume":"7","author":"Liu","year":"2008","journal-title":"Mol. Imaging"},{"key":"2026081809132851500_cit35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10549-009-0535-6","article-title":"A Dose- and Time-Controllable Syngeneic Animal Model of Breast Cancer Microcalcification","volume":"122","author":"Liu","year":"2010","journal-title":"Breast Cancer Res. Tr."},{"key":"2026081809132851500_cit36","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2310\/7290.2010.00050","article-title":"High-Resolution Computed Tomography of Single Breast Cancer Microcalcifications In Vivo","volume":"10","author":"Inoue","year":"2011","journal-title":"Mol. Imaging"},{"key":"2026081809132851500_cit37","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/00004424-199305000-00005","article-title":"Spatial Resolution in Digital Mammography","volume":"28","author":"Karssemeijer","year":"1993","journal-title":"Invest. Radiol."},{"key":"2026081809132851500_cit38","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1118\/1.2400830","article-title":"Evaluation of the Spatial Resolution Characteristics of a Cone-Beam Breast CT Scanner","volume":"34","author":"Kwan","year":"2007","journal-title":"Med. Phys."},{"key":"2026081809132851500_cit39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1097\/RLI.0b013e3182562ab9","article-title":"Effect of Computed Tomography Scanning Parameters on Gold Nanoparticle and Iodine Contrast","volume":"47","author":"Galper","year":"2012","journal-title":"Invest. Radiol."},{"key":"2026081809132851500_cit40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0169-409X(98)00105-7","article-title":"Delivery of Diagnostic Agents in Computed Tomography","volume":"37","author":"Krause","year":"1999","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026081809132851500_cit41","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1158\/1535-7163.MCT-06-0141","article-title":"Nanotechnology in Cancer Therapeutics: Bioconjugated Nanoparticles for Drug Delivery","volume":"5","author":"Sinha","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"2026081809132851500_cit42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1370\/afm.1466","article-title":"Long-Term Psychosocial Consequences of False-Positive Screening Mammography","volume":"11","author":"Brodersen","year":"2013","journal-title":"Ann. Fam. Med."},{"key":"2026081809132851500_cit43","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1097\/MLR.0b013e3181e57918","article-title":"Cost of Breast-Related Care in the Year Following False Positive Screening Mammograms","volume":"48","author":"Chubak","year":"2010","journal-title":"Med. Care"},{"key":"2026081809132851500_cit44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1148\/radiol.2251011667","article-title":"Comparison of the Performance of Screening Mammography, Physical Examination, and Breast US and Evaluation of Factors That Influence Them: An Analysis of 27,825 Patient Evaluations","volume":"225","author":"Kolb","year":"2002","journal-title":"Radiology"},{"key":"2026081809132851500_cit45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1056\/NEJMoa062790","article-title":"Mammographic Density and the Risk and Detection of Breast Cancer","volume":"356","author":"Boyd","year":"2007","journal-title":"New. Engl. J. Med."},{"key":"2026081809132851500_cit46","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.crad.2013.11.014","article-title":"What Effect Does Mammographic Breast Density Have on Lesion Detection in Digital Mammography?","volume":"69","author":"Mousa","year":"2014","journal-title":"Clin. Radiol."},{"key":"2026081809132851500_cit47","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1039\/C0CS00018C","article-title":"Biodistribution and Toxicity of Engineered Gold Nanoparticles: A Review of In Vitro and In Vivo Studies","volume":"40","author":"Khlebtsov","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"2026081809132851500_cit48","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1021\/mp300016p","article-title":"Role of Antibody-Mediated Tumor Targeting and Route of Administration in Nanoparticle Tumor Accumulation In Vivo","volume":"9","author":"Chattopadhyay","year":"2012","journal-title":"Mol. Pharmaceutics"},{"key":"2026081809132851500_cit49","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1073\/pnas.1219665110","article-title":"pHLIP Peptide Targets Nanogold Particles to Tumors","volume":"110","author":"Yao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081809132851500_cit50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/smll.200901006","article-title":"Sterilization Matters: Consequences of Different Sterilization Techniques on Gold Nanoparticles","volume":"6","author":"Franc\u0327a","year":"2010","journal-title":"Small"},{"key":"2026081809132851500_cit51","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1111\/j.1551-2916.2006.01067.x","article-title":"Kinetic Effects on Hydroxyapatite Whiskers Synthesized by the Chelate Decomposition Method","volume":"89","author":"Roeder","year":"2006","journal-title":"J. Am. Ceram. Soc."},{"key":"2026081809132851500_cit52","doi-asserted-by":"crossref","first-page":"R540","DOI":"10.1186\/bcr901","article-title":"Experimental Manipulation of Radiographic Density in Mouse Mammary Gland","volume":"6","author":"Hariri","year":"2004","journal-title":"Breast Cancer Res."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/nn5027802","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/8\/7\/7486\/14032731\/nn5027802.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/8\/7\/7486\/14032731\/nn5027802.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:26:23Z","timestamp":1787059583000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/8\/7\/7486\/1360801\/Contrast-Enhanced-X-ray-Detection-of-Breast"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,3]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2014,7,3]]},"published-print":{"date-parts":[[2014,7,22]]}},"URL":"https:\/\/doi.org\/10.1021\/nn5027802","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,3]]}}}