title: Molecular probes for imaging of hypoxia in the retina.
abstract: 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 >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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute , Nashville, Tennessee37232, United States.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Evans
authors.forename: Kwangho
authors.initials: K
authors.lastname: Kim
authors.forename: Chauca E
authors.initials: CE
authors.lastname: Moore
authors.forename: Md Imam
authors.initials: MI
authors.lastname: Uddin
authors.forename: Megan E
authors.initials: ME
authors.lastname: Capozzi
authors.forename: Jason R
authors.initials: JR
authors.lastname: Craft
authors.forename: Gary A
authors.initials: GA
authors.lastname: Sulikowski
authors.forename: Ashwath
authors.initials: A
authors.lastname: Jayagopal
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis* / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry; D009593:Nitroimidazoles / Q000737:chemistry; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D055351:Retinal Neurons / Q000473:pathology
chemical_list: D015335:Molecular Probes; D009593:Nitroimidazoles; C033815:pimonidazole; D016650:Fluorescein-5-isothiocyanate