NEAR INFRARED IMAGING OF MMP-2/MM-9 WITH A HIGHLY SPECIFIC OPTICAL PROBE

使用高度特异的光学探头对 MMP-2/MM-9 进行近红外成像

• 批准号: 7616539
• 负责人: Wilson Barry Edwards
• 金额: $ 17.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7616539
• 关键词: Accounting; Adjuvant Therapy; Amides; Animal Model; Basement membrane; Biological Assay; Breast; Cells; Cervix Uteri; Circular Dichroism Spectroscopy; Clinical Trials; Collagen; Collagen Type V; Diagnosis; Diagnostic Imaging; Dyes; Enzymes; Equipment; Extracellular Matrix Degradation; Fluorescence; Fluorescence Microscopy; Gelatinases; Genus Cola; Goals; Homo; Human; Hydrolysis; Image; Individual; Intervention; Life; Light; Lighting; Lung; Malignant Neoplasms; Mastication; Matrix Metalloproteinases; Measures; Mediating; Methods; Molecular; Molecular Sieve Chromatography; Monitor; Mus; Neoplasm Metastasis; Normal tissue morphology; Optics; Patients; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Primary Neoplasm; Prostate; Protease Inhibitor; Proteins; Relative (related person); Research; Resistance; Role; Sampling; Scanning; Serum; Skin Neoplasms; Solid; Source; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; Testing; Therapeutic Intervention; Thyroid Gland; Toxic effect; Treatment Efficacy; Xenograft procedure; angiogenesis; base; cancer diagnosis; cytotoxicity; design; in vivo; malignant breast neoplasm; melanoma; minimally invasive; mouse model; optical imaging; prognostic; protective effect; proteinase In; public health relevance; research study; subcutaneous; tumor; tumor progression

DESCRIPTION (provided by applicant): Matrix metallo-proteinases (MMPs) are often present in high levels in cancer such as tumors of the skin, breast, thyroid, cervix, lung, colon and prostate, but absent in normal tissues. MMPs are enzymes that are capable of chewing through the protein barriers that hold the primary tumor in its place. Once these barriers are degraded, the tumor can spread, or metastasize, throughout the body. We are designing a probe, to administer to the patient, that will remain invisible until it is degraded by the MMPs. After it is chewed in half, the probe will light up. We will capture and measure the light with optical imaging equipment and know that the tumor contains high levels of MMPs. The major pharmaceutical companies are currently developing drugs that will inhibit the action of the MMPs, thus slowing metastasis or stopping it altogether. If we are successful, the probe could be used to decide whether to initiate MMP inhibitor therapy and to monitor the therapy once it has begun. It could also be used to identify which tumors are likely to metastasize. The equipment used for optical imaging is relatively inexpensive and uncomplicated. A patient would likely be scanned at the office of their doctor. To test whether the probes will be effective in lighting up tumors we will perform the following Aims. Aim 1: The probes will be prepared from commercially available starting materials, separated from the starting materials if necessary, and tested for their purity Aim 2: Before testing in animal models, the probes will be tested in a variety of ways to show that they will indeed be chewed in half by MMPs and release the quantity of light needed to visualize a tumor growing in a living being. The stability and toxicity of the probes will be tested as well. Aim 3: Finally the probes will be tested in an animal model to see whether the tumors light up to an extent that the light is significant enough to be quantified. A variety of experiments (controls) will be used to make sure that the light observed is indeed due to MMP action and not from another source. PUBLIC HEALTH RELEVANCE The goal of this research is to develop pharmaceuticals that are optically invisible until they encounter a tumor and light up in its presence. Ultimately, these agents will allow for rapid and non-invasive or minimally invasive diagnosis of cancer.

描述（由申请人提供）：基质金属蛋白酶（MMP）通常在癌症中以高水平存在，例如皮肤、乳腺癌、甲状腺、子宫颈、肺、结肠和前列腺肿瘤，但在正常组织中不存在。 MMP 是一种酶，能够咀嚼将原发肿瘤固定在其位置的蛋白质屏障。一旦这些屏障被降解，肿瘤就会扩散或转移到全身。我们正在设计一种探针，用于对患者进行给药，在被 MMP 降解之前，该探针将保持不可见。咀嚼成两半后，探头会亮起。我们将用光学成像设备捕获和测量光，并知道肿瘤含有高水平的 MMP。主要制药公司目前正在开发抑制 MMP 作用的药物，从而减缓或完全阻止转移。如果我们成功，探针可用于决定是否启动 MMP 抑制剂治疗，并在治疗开始后对其进行监测。它还可用于识别哪些肿瘤可能转移。用于光学成像的设备相对便宜且简单。患者可能会在医生的办公室接受扫描。为了测试探针是否能有效照亮肿瘤，我们将执行以下目标。目标 1：探针将从市售起始材料中制备，必要时与起始材料分离，并测试其纯度。 目标 2：在动物模型中测试之前，将以多种方式测试探针，以证明它们确实会被 MMP 咀嚼成两半，并释放可视化生物体中生长的肿瘤所需的光量。探针的稳定性和毒性也将被测试。目标 3：最后将在动物模型中测试探针，看看肿瘤是否亮到足以进行量化的程度。将使用各种实验（对照）来确保观察到的光确实是由于 MMP 作用而不是来自其他来源。公共健康相关性 这项研究的目标是开发光学上不可见的药物，直到遇到肿瘤并在肿瘤存在时发光。最终，这些试剂将允许快速、无创或微创地诊断癌症。