Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization.
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 <italic<in vitro</italic< and by <italic<in vivo</italic< 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 <italic<in vivo</italic< for further validation as an imaging biomarker in retinal diseases.
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.
Md Jashim
MJ
Uddin
Vanderbilt University School of Medicine, Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Nashville, Tennessee 37232-6840, United States.
Chauca E
CE
Moore
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.
Brenda C
BC
Crews
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.
Cristina K
CK
Daniel
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.
Kebreab
K
Ghebreselasie
Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Department of Cancer Biology, Nashville, Tennessee 37232-6840, United States.
J Oliver
JO
McIntyre
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.
Lawrence J
LJ
Marnett
Vanderbilt University School of Medicine, Vanderbilt Eye Institute, Department of Ophthalmology and Visual Sciences, Nashville, Tennessee 37232-6840, United StatesdPharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel 4070, Switzerland.
Ashwath
A
Jayagopal
D000818:Animals; D020256:Choroidal Neovascularization / Q000000981:diagnostic imaging* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000378:metabolism; D005240:Feasibility Studies; D007091:Image Processing, Computer-Assisted; D007211:Indoles / Q000032:analysis / Q000737:chemistry*; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D012235:Rhodamines / Q000032:analysis / Q000737:chemistry*
D007211:Indoles; D012235:Rhodamines; C579286:fluorocoxib A; D051546:Cyclooxygenase 2