JBO Letters

Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization

[+] Author Affiliations
Md. Jashim Uddin, Brenda C. Crews, Cristina K. Daniel, Kebreab Ghebreselasie, Lawrence J. Marnett

Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Department of Biochemistry, Chemistry and Pharmacology, A. B. Hancock, Jr., Memorial Laboratory for Cancer Research, Nashville, Tennessee 37232-0146, United States

Chauca E. Moore

Vanderbilt University School of Medicine, Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Nashville, Tennessee 37232-6840, United States

J. Oliver McIntyre

Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Department of Cancer Biology, Nashville, Tennessee 37232-6840, United States

Ashwath Jayagopal

Vanderbilt University School of Medicine, Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Nashville, Tennessee 37232-6840, United States

Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel 4070, Switzerland

J. Biomed. Opt. 21(9), 090503 (Sep 14, 2016). doi:10.1117/1.JBO.21.9.090503
History: Received April 19, 2016; Accepted August 26, 2016
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Abstract.  Ocular angiogenesis is a blinding complication of age-related macular degeneration and other retinal vascular diseases. Clinical imaging approaches to detect inflammation prior to the onset of neovascularization in these diseases may enable early detection and timely therapeutic intervention. We demonstrate the feasibility of a previously developed cyclooxygenase-2 (COX-2) targeted molecular imaging probe, fluorocoxib A, for imaging retinal inflammation in a mouse model of laser-induced choroidal neovascularization. This imaging probe exhibited focal accumulation within laser-induced neovascular lesions, with minimal detection in proximal healthy tissue. The selectivity of the probe for COX-2 was validated in vitro and by in vivo retinal imaging with nontargeted 5-carboxy-X-rhodamine dye, and by blockade of the COX-2 active site with nonfluorescent celecoxib prior to injection of fluorocoxib A. Fluorocoxib A can be utilized for imaging COX-2 expression in vivo for further validation as an imaging biomarker in retinal diseases.

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© 2016 Society of Photo-Optical Instrumentation Engineers

Citation

Md. Jashim Uddin ; Chauca E. Moore ; Brenda C. Crews ; Cristina K. Daniel ; Kebreab Ghebreselasie, et al.
"Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization", J. Biomed. Opt. 21(9), 090503 (Sep 14, 2016). ; http://dx.doi.org/10.1117/1.JBO.21.9.090503


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