Near-infrared (NIR) fluorescent agent for in vivo imaging and other applications.
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Integrins are transmembrane cell surface receptors which mediate signal transduction, cell-to-cell interaction and cell-to extracellular matrix adhesion, key processes involved in angiogenesis, tumorigenesis and metastasis. Integrins have thus been hailed as clinically-relevant biomarkers of pathological conditions such as inflammation and tumor progression. The integrin avb3 is significantly upregulated in tumor cells and activated endothelial cells during neoangiogenesis.
IntegriSense™ 680 fluorescent imaging agent is used for in vivo detection of avb3 using a low molecular weight peptidomimetic antagonist coupled to a red fluorochrome. IntegriSense 680, an integrin-targeted molecular imaging agent allows the non-invasive imaging of disease status and progression. Pairing of an integrin antagonist treatment with IntegriSense 680 provides a mechanistic biomarker approach for assessing target coverage.
|Fluorescent Agent Type||Targeted|
|Optical Imaging Classification||Fluorescence Imaging|
|Product Brand Name||IntegriSense|
|Quantity in a Package Amount||1.0 Units|
|Therapeutic Area||Angiogenesis, Atherosclerosis, Oncology/Cancer|
|Unit Size||1 Vial (10 doses)|
|Wave Length||680 nm|
Current means of measuring disease in preclinical models of atherosclerosis include ex vivo assessment of disease tissues post-mortem and non-invasive imaging primarily of structural and anatomic features of lesions, in vivo. A non-invasive, quantitative means of imaging known biologic profiles associated with atherosclerotic disease, in vivo, would enable a robust additional understanding and analysis of disease progression and therapeutic response in research and drug development. We report the utility of the near infrared (NIR) protease-sensing, ProSense® 750 Fluorescent Pre-clinical Imaging Agent, in combination with the FMT® 2500 Quantitative Pre-clinical Imaging System for the non-invasive quantitative measurement of atherosclerotic disease biology and related response to therapy in apolipoprotein (apo) E-deficient mice in vivo. FMT (Fluorescence Molecular Tomography) imaging measured significant increases in aortic region protease activity with a range of values that were comparable to the range seen in the ex vivo aortic arches assessed by fluorescence reflectance imaging (FRI).
Integrins are a family of transmembrane glycoproteins which play a crucial role in the pathogenesis of various diseases, including cancer, and as such represent viable biomarkers for the progression of these diseases. We have developed IntegriSense 680, an integrin-targeted molecular imaging agent that allows the non-invasive imaging of disease status and progression.
Integrins are a family of transmembrane glycoproteins which play a crucial role in the pathogenesis of various diseases, including cancer, and as such represent viable biomarkers for the progression of these diseases. We have developed IntegriSense™ 680, an integrin-targeted molecular imaging agent that allows for the noninvasive imaging of disease status and progression. In breast and colorectal tumor imaging, this agent detects the integrin av+3 localized in the tumor.
Breast cancer is a clinical challenge today, with almost 200,000 new breast cancer cases reported annually in the United States alone. In 10% of breast cancer diagnoses, the cancer has metastasized to distant organs,in the body such as bone, liver, and lung, decreasing the 5-year relative survival rate to 20%. It is therefore essential to develop robust in vivo imaging approaches that can help dissect the metastatic process and,assist in the development of effective targeted therapeutic agents. Using imaging and agent approaches that are translatable from preclinical to clinical application further strengthens the utility of such efforts. To best establish robust imaging measures of the metastatic disease process in a model resembling clinical disease, we used 4T1 mouse breast adenocarcinoma cells injected intravenously into normal,immunologically-competent BALB/c mice. Three near infrared imaging agents, ProSense® 750 (PerkinElmer), a cathepsin-activatable agent,IntegriSense® 680 (PerkinElmer), an integrin-targeted agent and,AngioSense® 680 (PerkinElmer), a vascular agent, were injected IV to,detect the protease activity and vascular leak associated with aggressive,breast cancer growth. Disease-specific fluorescence was imaged and,quantified in living animals using the optical Fluorescence Molecular,Tomography – or FMTTM (FMT 2500TM quantitative tomography system,
IntegriSense 680 in vivo fluorescent imaging protocol
IntegriSense™ 680 is a targeted fluorescence imaging agent comprising a potent, selective non-peptide small molecule integrin avß3 antagonist and an NIR fluorochrome. This agent has been developed to enable in vivo visualization and quantification of integrin avß3 expression in neovasculature as well as in tumor cells, to monitor tumor angiogenesis, growth and treatment efficacy.