Fluorescence lifetime tomography of tumor physiology in small animals

小动物肿瘤生理学的荧光寿命断层扫描

• 批准号: 8531929
• 负责人: Anand T.N. Kumar
• 金额: $ 35.98万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531929
• 关键词: Algorithms; Angiogenesis Inhibitors; Animal Model; Animals; Antineoplastic Agents; Blood Vessels; Blood Volume; Breast Cancer Cell; Cancer Cell Growth; Cancer Diagnostics; Cessation of life; Clinical Trials; Custom; Detection; Development; Drug Delivery Systems; ERBB2 gene; Early Diagnosis; Epidermal Growth Factor Receptor; Fluorescence; Goals; Human; Image; Lasers; Life; Longitudinal Studies; Malignant Neoplasms; Measurement; Microscopy; Modeling; Monitor; Mus; Neoplasm Metastasis; Optics; Oxygen; Physiologic pulse; Physiological; Physiology; Play; Prevention; Process; Proteins; Resolution; Roche brand of trastuzumab; Role; Spectrum Analysis; Staging; System; Techniques; Technology; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Time; Tissues; Tumor Oxygenation; Tumor Volume; Validation; Visual; angiogenesis; base; cancer cell; cancer imaging; cancer therapy; design; drug discovery; fluorophore; in vivo; insight; instrumentation; intravital microscopy; malignant breast neoplasm; novel; optical imaging; pre-clinical; pre-clinical research; reconstruction; red fluorescent protein; tomography; tumor; tumor growth; tumor microenvironment; whole body imaging

ABSTRACT: The goal of this proposal is to advance an optical imaging system for longitudinal, high throughput small animal cancer imaging using fluorescence lifetime contrast. We will specifically advance and validate a novel time domain (TD) lifetime- based tomography technique for whole-body imaging of two important and related phenomena, namely tumor metastasis and angiogenesis. We will first enable whole animal imaging of metastasis using fluorescent proteins (FPs) in the visible spectrum (450nm - 650nm). Lifetime imaging of FPs will be applied to track metastasis in a small animal model of human breast cancer. This will allow longitudinal quantification of metastatic foci in living mice at earlier stages than currently possible with other non- invasive techniques. We will next employ near infra-red (NIR) (650nm - 850nm) fluorophores with distinct lifetimes to study angiogenesis and drug delivery during therapy. Optical imaging can enable rapid, deep tissue (> 1 cm) imaging of the entire tumor volume with mm-scale resolution, which can allow global quantitative readouts of tumor physiology under therapeutic intervention. Optical imaging also allows a unique opportunity for simultaneously tracking multiple processes within the tumor volume using multiple fluorophores with distinct lifetimes (lifetime "multiplexing"). We will validate lifetime multiplexing to track angiogenesis and drug delivery to tumors simultaneously. In order to achieve this, we will use a NIR fluorophore that targets vasculature and a second NIR fluorophore with distinct lifetime that is tagged to herceptin. Herceptin is an anti-angiogenic and therapeutic agent that targets the human epidermal growth factor receptor 2 (HER2/neu), which is over-expressed in human breast cancers. Additionally, NIR spectroscopy of intrinsic tissue optical contrast will reveal changes in tumor blood volume and oxygenation due to therapy, and FP expressing cancer cells will reveal tumor growth. By enabling simultaneous monitoring of multiple physiological markers in the entire volume of tumor, this technology will provide new insights into the interplay between angiogenesis and drug delivery during herceptin treatment, and will allow the validation and optimization of developmental cancer drugs.

摘要：本课题的目标是研制一种用于激光成像的光学成像系统