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This study describes the design and preparation of an innovative pair of K\u2010edge metal nanoprobes and demonstrates the feasibility of their simultaneous quantitative detection using spectral photon\u2010counting computed tomography (SPCCT). Glycosaminoglycan (GAG) capped nanoparticles (ca. 15\u201320\u00a0nm) targeting two distinct components of the cartilage tissue, namely, aggrecan (acan) and aggrecanase (acanase) are designed and synthesized. These targeted nanoparticles comprised of praseodymium (Pr) and hafnium (Hf), with well\u2010separated K\u2010edge energies, enable simultaneous and ratiometric imaging of dual biomarkers in cartilage tissue. Following extensive physico\u2010chemical characterization of the ligand\u2010targeted particles, the feasibility of homing dual biomarkers in vitro is demonstrated. The material discrimination and simultaneous quantification of these targeted particles are also achieved and corroborated with inductively coupled plasmon spectroscopy. For the first time, the use of praseodymium is reported as a contrast agent for SPCCT imaging and demonstrates the ability to pair it with hafnium nanoprobes for multicontrast imaging of diseases. Importantly, the potential for ratiometric molecular imaging and tracking of osteoarthritis (OA) progression is shown with SPCCT K\u2010edge based imaging approach.<\/jats:p>","DOI":"10.1002\/advs.202408408","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T10:44:20Z","timestamp":1728297860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted K\u2010Edge Nanoprobes From Praseodymium and Hafnium for Ratiometric Tracking of Dual Biomarkers using Spectral Photon Counting CT"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4939-1658","authenticated-orcid":false,"given":"Nivetha","family":"Gunaseelan","sequence":"first","affiliation":[{"name":"Huck Institutes of the Life Sciences Department(s) of Biomedical Engineering Nuclear Engineering Materials Science and Engineering The Pennsylvania State University  101 Huck Life Sciences Building University Park PA 16802 USA"},{"name":"Department of Pediatrics Centre for Blood Oxygen Transport &amp; 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