Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer.

Overexpression of cyclooxygenase-1 (COX-1) is associated with the initiation and progression of ovarian cancer, and targeted imaging of COX-1 is a promising strategy for early detection of this disease. We report the discovery of -[(5-carboxy-X-rhodaminyl)but-4-yl]-3-(1-(4-methoxyphenyl)-5-(-tolyl)-1-pyrazol-3-yl)propenamide (CMP) as the first COX-1-targeted optical agent for imaging of ovarian cancer. CMP exhibits light emission at 604 nm (λ), thereby minimizing tissue autofluorescence interference.

Discovery of Furanone-Based Radiopharmaceuticals for Diagnostic Targeting of COX-1 in Ovarian Cancer.

In vivo targeting and visualization of cyclooxygenase-1 (COX-1) using multimodal positron emission tomography/computed tomography imaging represents a unique opportunity for early detection and/or therapeutic evaluation of ovarian cancer because overexpression of COX-1 has been characterized as a pathologic hallmark of the initiation and progression of this disease. The furanone core is a common building block of many synthetic and natural products that exhibit a wide range of biological activities. We hypothesize that furanone-based COX-1 inhibitors can be designed as imaging agents for the early detection, delineation of tumor margin, and evaluation of treatment response of ovarian cancer.

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.

Antitumor Activity of Cytotoxic Cyclooxygenase-2 Inhibitors.

Targeted delivery of chemotherapeutic agents to tumors has been explored as a means to increase the selectivity and potency of cytotoxicity. Most efforts in this area have exploited the molecular recognition of proteins highly expressed on the surface of cancer cells followed by internalization. A related approach that has received less attention is the targeting of intracellular proteins by ligands conjugated to anticancer drugs.

Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe.

Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a range of diagnostic and therapeutic settings. We report a near-infrared COX-2-targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical imaging. FC exhibits selective and potent COX-2 inhibition in both purified protein and human cancercell lines.

Trifluoromethyl fluorocoxib a detects cyclooxygenase-2 expression in inflammatory tissues and human tumor xenografts.

Fluorocoxib A is an effective COX-2-targeted optical imaging agent, used for in vivo detection of inflammatory tissues and premalignant and malignant tumors that express elevated levels of COX-2 (Uddin et al. Cancer Res. 2010, 70, 3618-3627).

PET radiotracer [¹⁸F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: preliminary investigation.

Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound.