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: 8332829
• 负责人: Anand T.N. Kumar
• 金额: $ 37.64万
• 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/8332829
• 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; 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：该方案的目标是推进一种光学成像系统，用于 基于荧光寿命的纵向高通量小动物肿瘤成像 对比度。我们将特别提出并验证一种新的时间域(TD)寿命- 基于层析成像技术的两个重要和相关的全身成像 这些现象，即肿瘤转移和血管生成。我们将首先启用 利用可见光谱荧光蛋白对肿瘤转移的动物成像 (450 nm-650 nm)。FPS的寿命成像将应用于追踪小鼠的转移 人乳腺癌的动物模型。这将允许纵向量化 活着的小鼠的转移灶比目前其他非小鼠的转移灶更早 侵入性技术。接下来我们将采用近红外线(NIR)(650 nm-850 nm) 具有不同寿命的荧光团研究血管生成和药物输送 心理治疗。光学成像可以快速、深层组织(&gt；1厘米)成像整个 具有毫米级分辨率的肿瘤体积，这可以使全球定量读出 治疗干预下的肿瘤生理学。光学成像还允许独一无二的 同时跟踪肿瘤体积内的多个过程的机会 具有不同寿命的多个荧光团(寿命“多路传输”)。我们将验证 终身多路复用法，以同时跟踪血管生成和向肿瘤的药物输送。在……里面 为了实现这一点，我们将使用针对血管系统和 标记在赫赛汀上的第二个具有独特寿命的近红外荧光团。赫赛汀是一种 靶向人表皮生长因子的抗血管生成和治疗剂 受体2(HER2/neu)，在人类乳腺癌中过度表达。另外， 组织内部光学对比度的近红外光谱将揭示肿瘤血液的变化 治疗引起的体积和氧合，以及表达FP的癌细胞将揭示 肿瘤生长。通过实现对多个生理标志物的同时监测 整个肿瘤体积，这项技术将为相互作用提供新的见解 在赫赛汀治疗期间血管生成和药物释放之间的关系，并将允许 发育性抗癌药物的验证和优化。