{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:15:30Z","timestamp":1788416130083,"version":"build-2803163510"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T00:00:00Z","timestamp":1443052800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY008126"],"award-info":[{"award-number":["P30EY008126"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY023397"],"award-info":[{"award-number":["R01EY023397"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001694","name":"International Retinal Research Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxia has been associated with retinal diseases which lead the causes of irreversible vision loss, including diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. Therefore, technologies for imaging hypoxia in the retina are needed for early disease detection, monitoring of disease progression, and assessment of therapeutic responses in the patient. Toward this goal, we developed two hypoxia-sensitive imaging agents based on nitroimidazoles which are capable of accumulating in hypoxic cells in vivo. 2-nitroimidazole or Pimonidazole was conjugated to fluorescent dyes to yield the imaging agents HYPOX-1 and HYPOX-2. Imaging agents were characterized in cell culture and animal models of retinal vascular diseases which exhibit hypoxia. Both HYPOX-1 and -2 were capable of detecting hypoxia in cell culture models with &amp;gt;10:1 signal-to-noise ratios without acute toxicity. Furthermore, intraocular administration of contrast agents in mouse models of retinal hypoxia enabled ex vivo detection of hypoxic tissue. These imaging agents are a promising step toward translation of hypoxia-sensitive molecular imaging agents in preclinical animal models and patients.<\/jats:p>","DOI":"10.1021\/bc500400z","type":"journal-article","created":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T10:22:26Z","timestamp":1411554146000},"page":"2030-2037","source":"Crossref","is-referenced-by-count":40,"title":["Molecular Probes for Imaging of Hypoxia in the Retina"],"prefix":"10.1021","volume":"25","author":[{"given":"Stephanie M.","family":"Evans","sequence":"first","affiliation":[{"name":"Vanderbilt Eye Institute , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangho","family":"Kim","sequence":"additional","affiliation":[{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37235"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chauca E.","family":"Moore","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Imam","family":"Uddin","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Capozzi","sequence":"additional","affiliation":[{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37235"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Craft","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A.","family":"Sulikowski","sequence":"additional","affiliation":[{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37235"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwath","family":"Jayagopal","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37235"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,9,24]]},"reference":[{"key":"2026090301354724100_cit1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S0014-4835(03)00213-6","article-title":"The blood-retinal\nbarriers system. Basic concepts and clinical evaluation","volume":"78","author":"Cunha-Vaz","year":"2004","journal-title":"Exp. Eye Res."},{"key":"2026090301354724100_cit2","first-page":"1647","article-title":"Retinal hypoxia\nin long-term diabetic cats","volume":"39","author":"Linsenmeier","year":"1998","journal-title":"Invest. Ophthalmol.\nVis. Sci."},{"key":"2026090301354724100_cit3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1172\/JCI0213776","article-title":"Acute intensive insulin therapy exacerbates\ndiabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha\nand VEGF","volume":"109","author":"Poulaki","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2026090301354724100_cit4","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1167\/iovs.04-1050","article-title":"Reduced\nfoveolar choroidal blood flow in eyes with increasing AMD severity","volume":"46","author":"Grunwald","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090301354724100_cit5","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1136\/bjo.2005.082974","article-title":"Effect of systemic\nhypertension on foveolar choroidal blood flow in age related macular\ndegeneration","volume":"90","author":"Metelitsina","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"2026090301354724100_cit6","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1167\/iovs.12-11284","article-title":"Spectrophotometric retinal oximetry\nin pigs","volume":"54","author":"Traustason","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090301354724100_cit7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1755-3768.2012.02393.x","article-title":"Retinal oximetry\nin central retinal artery occlusion","volume":"91","author":"Hardarson","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"2026090301354724100_cit8","doi-asserted-by":"crossref","first-page":"054015","DOI":"10.1117\/1.2976032","article-title":"Retinal vessel\noximetry-calibration, compensation for vessel diameter and fundus\npigmentation, and reproducibility","volume":"13","author":"Hammer","year":"2008","journal-title":"J. Biomed.\nOpt."},{"key":"2026090301354724100_cit9","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1167\/iovs.06-0039","article-title":"Automatic\nretinal oximetry","volume":"47","author":"Hardarson","year":"2006","journal-title":"Invest.\nOphthalmol. Vis. Sci."},{"key":"2026090301354724100_cit10","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1167\/iovs.12-10507","article-title":"Choroidal oximetry with a noninvasive\nspectrophotometric oximeter","volume":"54","author":"Kristjansdottir","year":"2013","journal-title":"Invest. Ophthalmol.\nVis. Sci."},{"key":"2026090301354724100_cit11","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.1167\/iovs.13-11887","article-title":"Inner retinal oxygen\ndelivery and metabolism under normoxia and hypoxia in rat","volume":"54","author":"Wanek","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090301354724100_cit12","doi-asserted-by":"crossref","first-page":"7998","DOI":"10.1167\/iovs.13-12318","article-title":"Absolute retinal blood\nflow measurement with a dual-beam Doppler optical coherence tomography","volume":"54","author":"Dai","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090301354724100_cit13","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0360-3016(00)00787-2","article-title":"Changes in tumor hypoxia measured with a double hypoxic\nmarker technique","volume":"48","author":"Ljungkvist","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol.\nPhys."},{"key":"2026090301354724100_cit14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1006\/gyno.1998.5163","article-title":"Pimonidazole: a\nnovel hypoxia marker for complementary study of tumor hypoxia and\ncell proliferation in cervical carcinoma","volume":"71","author":"Varia","year":"1998","journal-title":"Gynecol.\nOncol."},{"key":"2026090301354724100_cit15","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1046\/j.1432-1327.1998.2530743.x","article-title":"Reductive metabolism of the hypoxia\nmarker Pimonidazole is regulated by oxygen tension independent of\nthe pyridine nucleotide redox state","volume":"253","author":"Arteel","year":"1998","journal-title":"Eur. J.\nBiochem."},{"key":"2026090301354724100_cit16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0167-8140(03)00010-0","article-title":"Measurements of\nhypoxia using Pimonidazole and polarographic\noxygen-sensitive electrodes in human cervix carcinomas","volume":"67","author":"Nordsmark","year":"2003","journal-title":"Radiother. Oncol."},{"key":"2026090301354724100_cit17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/BF02723034","article-title":"Establishment\nof an E1A-immortalized retinal cell culture","volume":"32","author":"Seigel","year":"1996","journal-title":"In Vitro Cell. Dev. Biol.: Anim."},{"key":"2026090301354724100_cit18","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11626-997-0091-5","article-title":"Recoverin\nexpression in the R28 retinal precursor cell line","volume":"33","author":"Seigel","year":"1997","journal-title":"In Vitro Cell. Dev. Biol.: Anim."},{"key":"2026090301354724100_cit19","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1167\/iovs.14-14216","article-title":"The role of cytochrome\nP450 epoxygenases\nin retinal angiogenesis","volume":"55","author":"Capozzi","year":"2014","journal-title":"Invest. Ophthalmol.\nVis. Sci."},{"key":"2026090301354724100_cit20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.preteyeres.2008.05.001","article-title":"Vascular endothelial\ngrowth factor in eye disease","volume":"27","author":"Penn","year":"2008","journal-title":"Prog. Retin. Eye\nRes."},{"key":"2026090301354724100_cit21","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/aps.2011.24","article-title":"Inhibition of hypoxia-inducible\ncarbonic anhydrase-IX\nenhances hexokinase II inhibitor-induced hepatocellular carcinoma\ncell apoptosis","volume":"32","author":"Yu","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"2026090301354724100_cit22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.radonc.2006.08.010","article-title":"Pimonidazole labelling and response\nto fractionated\nirradiation of five human squamous cell carcinoma (hSCC) lines in\nnude mice: the need for a multivariate approach in biomarker studies","volume":"81","author":"Yaromina","year":"2006","journal-title":"Radiother. Oncol."},{"key":"2026090301354724100_cit23","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0360-3016(00)01493-0","article-title":"Invasive oxygen measurements and\nPimonidazole labeling in human cervix carcinoma","volume":"49","author":"Nordsmark","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"2026090301354724100_cit24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1001\/archopht.1967.00980030457009","article-title":"A combined technique\nof fluorescein funduscopy and angiography of the eye","volume":"78","author":"Gass","year":"1967","journal-title":"Arch. Ophthalmol."},{"key":"2026090301354724100_cit25","first-page":"101","article-title":"Oxygen-induced retinopathy in the\nmouse","volume":"35","author":"Smith","year":"1994","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090301354724100_cit26","doi-asserted-by":"crossref","first-page":"e11103","DOI":"10.1371\/journal.pone.0011103","article-title":"HIF-1alpha\nand HIF-2alpha are differentially activated\nin distinct cell populations in retinal ischaemia","volume":"5","author":"Mowat","year":"2010","journal-title":"PLoS One"},{"key":"2026090301354724100_cit27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.exer.2014.03.010","article-title":"Correspondence\nof retinal thinning and vasculopathy in mice with oxygen-induced retinopathy","volume":"122","author":"Mezu-Ndubuisi","year":"2014","journal-title":"Exp. Eye Res."},{"key":"2026090301354724100_cit28","doi-asserted-by":"crossref","first-page":"13028","DOI":"10.1002\/anie.201305784","article-title":"Development of azo-based fluorescent\nprobes to detect different levels of hypoxia","volume":"52","author":"Piao","year":"2013","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090301354724100_cit29","doi-asserted-by":"crossref","first-page":"15846","DOI":"10.1021\/ja105937q","article-title":"Hypoxia-sensitive fluorescent probes\nfor in vivo real-time fluorescence imaging of acute ischemia","volume":"132","author":"Kiyose","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"2026090301354724100_cit30","doi-asserted-by":"crossref","first-page":"19588","DOI":"10.1021\/ja310049d","article-title":"Reversible off-on fluorescence probe for hypoxia and\nimaging of hypoxia-normoxia cycles in live cells","volume":"134","author":"Takahashi","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"2026090301354724100_cit31","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.ijrobp.2011.04.027","article-title":"Impact of hypoxia on the metastatic potential of human\nprostate cancer cells","volume":"81","author":"Dai","year":"2011","journal-title":"Int. J. Radiat. Oncol.\nBiol. Phys."}],"container-title":["Bioconjugate Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/bc500400z","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/11\/2030\/7861637\/bc500400z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/11\/2030\/7861637\/bc500400z.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:35:57Z","timestamp":1788413757000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bcches\/article\/25\/11\/2030\/771824\/Molecular-Probes-for-Imaging-of-Hypoxia-in-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,24]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,9,24]]},"published-print":{"date-parts":[[2014,11,19]]}},"URL":"https:\/\/doi.org\/10.1021\/bc500400z","relation":{},"ISSN":["1043-1802","1520-4812"],"issn-type":[{"value":"1043-1802","type":"print"},{"value":"1520-4812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,24]]}}}