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Precise zinc homeostasis, maintained by a complex interplay of transporters, storage proteins, and regulatory mechanisms, is critical for cellular function and organismal health. Disrupted zinc homeostasis has been implicated in the pathophysiology of diabetes, neurodegenerative disorders, and cancers, through alterations in zinc-dependent signaling pathways, oxidative stress responses, and apoptosis mechanisms. Thus, zinc biodistribution is a potential biomarker enabling improved detection of zinc-related pathologies, assessment of disease prognosis, and development of more targeted prevention strategies. While fluorescence techniques have advanced our understanding of cellular zinc, their application in human studies remains restricted. This highlights the need for zinc-specific biosensors that can be integrated with clinical imaging technologies, such as Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI), to enable in vivo visualization of zinc distribution and dynamics. This review describes the mechanistic understanding of zinc-associated diseases, details the design principles of molecular zinc biosensors (including radiopharmaceuticals and MRI contrast agents), and identifies the challenges and future directions for developing more specific and sensitive probes. For nuclear imaging (PET and SPECT), this includes probes utilizing radioactive zinc ions 65Zn, 62Zn, and 63Zn, and zinc chelators labeled with isotopes like 18F, 11C, and 125I. For MRI, detection mechanisms leverage relaxivity (r1), Chemical Exchange Saturation Transfer (CEST), and hyperpolarization technologies. These imaging modalities exhibit the potential of bridging the gap between cellular and systemic zinc organ-level dynamics, offering a \u201chorizontal\u201d perspective on disease pathogenesis and facilitating precision medicine.<\/jats:p>","DOI":"10.1021\/cbmi.5c00264","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:39:57Z","timestamp":1778686797000},"page":"1886-1914","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Imaging of\nIn Vivo Zinc Distribution Using\nNuclear and Magnetic Resonance Imaging"],"prefix":"10.1021","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-0133","authenticated-orcid":true,"given":"Changhua","family":"Mu","sequence":"first","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Liu","sequence":"additional","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umama","family":"Ali","sequence":"additional","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peder E. Z.","family":"Larson","sequence":"additional","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94107"]},{"name":"University of California , , , ,","place":["San Francisco, California, United States, 94158"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9999-8226","authenticated-orcid":true,"given":"Sunita P.","family":"Ho","sequence":"additional","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94143"]},{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94143"]},{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94143"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8694-1199","authenticated-orcid":true,"given":"Robert R.","family":"Flavell","sequence":"additional","affiliation":[{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94107"]},{"name":"University of California , , , ,","place":["San Francisco, California, United States, 94158"]},{"name":"University of California, San Francisco , , , ,","place":["San Francisco, California, United States, 94158"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"issue":"1\u201312","key":"2026092808074860400_cit1","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.3390\/ijms18112285","article-title":"Zinc in cellular\nregulation: the nature and significance of \u201czinc signals\u201d","volume":"18","author":"Maret","year":"2017","journal-title":"Int. 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