Fluorescence Imaging to Optimize Cancer Therapy

荧光成像优化癌症治疗

• 批准号: 6925872
• 负责人: Brian W. Pogue
• 金额: $ 31.56万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925872
• 关键词: angiography; bioimaging /biomedical imaging; biomarker; cell line; cellular respiration; fluorescent dye /probe; indocyanine green; ketoacid; laboratory rat; metabolism; mitochondria; molecular /cellular imaging; neoplasm /cancer photoradiation therapy; neoplasm /cancer radiodiagnosis; oxygen transport; photosensitizing agents; porphyrins; respiratory oxygenation; therapy adverse effect

DESCRIPTION (provided by applicant): The use of optical methods for imaging and treatment of cancer is growing rapidly, largely because they work well in the setting of early detection methods, treatment of pre-malignancies or as an adjuvant treatment. Optically active agents can provide a molecular-specific or site-specific localization in tumors, and in this work we exploit both of these for diagnostic and therapeutic use. In particular, we focus on aminolevulinic acid, which induces production of protoporphyrin IX (PPIX) in the mitochondria of cells, thereby providing both a diagnostic measure of cellular metabolism as well as a way to strategically cause photodynamic damage at this site. We will use two technologically advanced approaches to quantifying the fluorescence in vivo, including our tissue micro-sampling probe and our near-infrared tomographic instrumentation. We will systematically examine the optimal way to measure fluorescence from PPIX in tumors, using needle measurements, diffuse probe measurements and diffuse tomography imaging of tissue. We will use the optimal solution in several specific biological hypotheses. First in diagnostic use, we will examine how the production of PPIX is related to the growth rate of cancer cells, focusing on the multiple cell lines available in the Dunning prostate tumor. This will also help to explore the feasibility of using repeated dosing in imaging, and examining how this affects the measurements. For therapeutic targeting, we will use the imaging system to help us explore a novel targeting approach that we have developed, which synergistically combines photodynamic pre-treatment with radiation therapy. We have found that damage to the mitochondria causes acute respiration shut down, reducing the consumption of oxygen and providing a good way to increase the oxygenation in tumors. This effect was combined with single dose radiation therapy and was found to increase the efficacy of tumor destruction. In this study, we will further examine this effect focusing on exploiting the potential for fractionated delivery of both therapies. Since ALA-PPIX provides a proportionate measure of the cellular metabolic rate, we will use the fluorescence from PPIX as a diagnostic measure of cellular activity, while using indocyanine green fluorescence as a measure of the vascular volume of the tissue. Both can be quantified in the same tissue by appropriate filtering and sequencing of the light signals, and this combined imaging approach will be examined for reliability of monitoring vascular versus cellular damage in vivo.

描述（由申请人提供）： 使用光学方法对癌症进行成像和治疗的使用迅速增长，这主要是因为它们在早期检测方法，治疗前的治疗方法或作为辅助治疗方面效果很好。光学活性剂可以在肿瘤中提供分子特异性或特定于位点的定位，在这项工作中，我们利用这两者用于诊断和治疗用途。特别是，我们专注于氨基乙烯酸，该氨基乙烯酸诱导细胞线粒体中原核IX（PPIX）的产生，从而提供了细胞代谢的诊断度量，也提供了在该站点在战略上造成光学损害的诊断方法。我们将使用两种技术先进的方法来量化体内荧光，包括我们的组织微采样探针和近红外层析成像仪器。我们将系统地检查使用针头测量，扩散探针测量和组织的弥漫性层析成像成像的最佳方法来测量肿瘤中PPIX的荧光。我们将在几种特定的生物学假设中使用最佳解决方案。首先，在诊断使用中，我们将研究PPIX的产生与癌细胞的生长速率如何相关，重点是Dunning Prostate肿瘤中可用的多个细胞系。这也将有助于探索在成像中使用重复给药的可行性，并检查这如何影响测量结果。对于治疗靶向，我们将使用成像系统来帮助我们探索一种新型的定位方法，该方法协同将光动力学的预处理与放射疗法结合在一起。我们发现，对线粒体的损​​害会导致急性呼吸关闭，减少氧气的消耗，并提供一种增加肿瘤中氧合的好方法。这种作用与单剂量放射疗法结合使用，发现增加了肿瘤破坏的功效。在这项研究中，我们将进一步研究这种效果，侧重于利用两种疗法的分离递送的潜力。由于ALA-PPIX提供了对细胞代谢率的比例度量，因此我们将使用PPIX的荧光作为细胞活性的诊断度量，同时使用吲哚氰胺绿色荧光作为组织血管体积的量度。可以通过适当的过滤和测序光信号在同一组织中量化两者，并且将检查这种组合成像方法的可靠性，以监测体内血管与细胞损伤的可靠性。