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Near-IR Bioluminescence Imaging

近红外生物发光成像

基本信息

批准号：
7617115
负责人：
STEPHEN C. MILLER
金额：
$ 21.94万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7617115
关键词：
Animals Arsenicals Bioluminescence Blood Body cavities Cell Count Cells Chemicals Cultured Cells Detection Development Disease Progression Dyes Energy Transfer Evaluation Firefly Luciferases Gene Expression Profiling Generations Genomics Hand Hemoglobin Image Imaging Techniques Intervention Life Light Luciferases Luminescent Proteins Magnetic Resonance Imaging Malignant Epithelial Cell Methods Monitor Mus Neoplasm Metastasis Optics Order Coleoptera Organ Output Penetration Pharmaceutical Preparations Photochemistry Positron-Emission Tomography Property Proteins Relative (related person)Research Personnel Resolution Specialist Speed Technology Therapeutic Tissues Travel Validation Visible Radiation Whole Organism Work absorption anti-cancer therapeutic body cavity cancer cell cancer imaging cancer therapy cell growth cost data acquisition fluorophore high throughput screening imaging modality improved in vivo light emission luciferin neoplastic cell novel protein degradation protein protein interaction response small molecule therapeutic protein therapeutic target tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Bioluminescent imaging (BLI) with firefly luciferase has gained widespread acceptance as a powerful, inexpensive, and non-invasive method to monitor gene expression, enzymatic activity, protein-protein interactions and protein degradation in the context of the whole organism. Relative to other imaging modalities such as PET and MRI, bioluminescence imaging has the advantages of low cost, speed, sensitivity, high throughput and ease of use by non-specialists. These advantages make BLI the method of choice for rapidly assessing tumor progression and response to potential therapeutics. The major limitation of BLI is the poor penetration of visible light through tissue. Illuminated tissue is most transparent to near-IR light (650-900 nm), where autofluorescence, scattering, and the absorption of visible light by hemoglobin is minimal. Despite considerable effort spent isolating and mutagenizing luminescent proteins, there is no luciferase that maximally emits light >650 nm. We propose two synergistic approaches to shift the light output of firefly luciferase to the near-IR: 1) Resonance energy transfer to a targetable near-IR fluorophore, and 2) Synthesis of novel luciferin substrates that maximally emit light at longer wavelengths. These aims are relevant to in vivo cancer imaging because they will improve the speed, detection limit, and depth penetration of bioluminescence imaging. Introduction of cancer cells that express light-emitting proteins into mice has allowed researchers to monitor cancer progression and response to drug treatment in living animals. However, the emitted light is strongly absorbed by blood, and thus does not travel far through the mouse. We are changing the wavelength of the emitted light to avoid absorption by blood and allow deeper penetration of the light through the mouse, improving our ability to detect small tumors or tumors in deep organs.

描述（由申请人提供）：使用萤火虫荧光素酶的生物发光成像（BLI）作为监测整个生物体背景下的基因表达、酶活性、蛋白质-蛋白质相互作用和蛋白质降解的强大、廉价和非侵入性方法已获得广泛认可。相对于PET和MRI等其他成像方式，生物发光成像具有成本低、速度快、灵敏度高、通量高和非专业人员易于使用等优点。这些优势使BLI成为快速评估肿瘤进展和对潜在疗法反应的首选方法。BLI的主要限制是可见光通过组织的穿透性差。受照组织对近红外光（650-900 nm）最透明，其中自体荧光、散射和血红蛋白对可见光的吸收最小。尽管在分离和诱变发光蛋白上花费了相当大的努力，但没有最大发射>650 nm的光的荧光素酶。我们提出了两种协同方法来将萤火虫荧光素酶的光输出转移到近红外：1）共振能量转移到可靶向的近红外荧光团，以及2）合成最大限度地发射较长波长光的新型荧光素底物。这些目标与体内癌症成像相关，因为它们将提高生物发光成像的速度、检测限和深度穿透。将表达发光蛋白的癌细胞引入小鼠体内，使研究人员能够监测活体动物的癌症进展和对药物治疗的反应。然而，发射的光被血液强烈吸收，因此不会通过小鼠传播很远。我们正在改变发射光的波长，以避免被血液吸收，并允许光更深地穿透小鼠，提高我们检测小肿瘤或深部器官肿瘤的能力。