Molecular optical coherence tomography for monitoring cancer therapy

项目概述：本项目的目标是开发一种新的分子成像技术，光热光学相干断层扫描（光热OCT），并将该技术与现有的OCT技术（多普勒OCT）一起用于监测癌症治疗。光热和多普勒OCT联合成像具有高分辨率、化学特异性、血流成像能力和相对较高的穿透深度，将成为监测血管对抗血管生成药物反应的有力工具。本工作的第一个目的是开发和验证一个光热OCT系统，该系统使用激光加热的金纳米壳作为光热源，用于类组织幻影。光热OCT系统将包括一个现有的多普勒OCT系统和一个调幅近红外（NIR）加热激光器。含有吸收近红外（光在组织中穿透最深的光学窗口）的金纳米壳的模型，聚苯乙烯球作为散射体，血红蛋白作为吸收体，将被用来表征在类组织环境中来自金纳米壳的光热信号。第二个目的是测试多普勒OCT在动物模型中测量肿瘤微血管流速变化对抗血管生成药物的反应的潜力。血管内皮生长因子（VEGF）是一种血管生成因子，在某些类型的癌症中过度表达。贝伐单抗是一种抗人VEGF抗体，可诱导实体瘤患者的肿瘤缩小。实时多普勒OCT（一项现有技术）将用于贝伐单抗治疗前和贝伐单抗治疗后特定时间点在背皮瓣小鼠窗室模型中生长的结肠癌肿瘤微血管流速的成像，以及未接受贝伐单抗治疗的对照动物。本研究的第三个也是最后一个目的是测试光热和多普勒OCT联合成像在体内抗血管生成药物作用下肿瘤微血管VEGF水平和血流速率的潜力。与抗VEGF受体的抗体结合的金纳米壳将被静脉注射到小鼠的肿瘤血管中。光热OCT和多普勒OCT将分别用于对照动物和贝伐单抗治疗前和贝伐单抗治疗后不同时间点VEGF受体的数量和分布以及微血管流速的成像。相关性：大多数癌症死亡是由于转移性疾病对化疗药物没有反应。本研究为动物模型中肿瘤对肿瘤治疗反应的监测和研究提供了一种微创方法。在未来，这项技术可以为癌症患者提供个性化的护理，从而降低癌症的发病率和死亡率。

DESCRIPTION (provided by applicant): Project Summary: The objective of the proposed work is to develop a novel molecular imaging technique, photothermal optical coherence tomography (photothermal OCT), and use this technology along with existing OCT technologies (Doppler OCT) to monitor cancer therapy. Combined photothermal and Doppler OCT would be a powerful tool to monitor the vascular response to anti-angiogenic drugs, due to its high resolution, chemical specificity, flow imaging capabilities and relatively high penetration depths. The first aim of this work is to develop and validate a photothermal OCT system with laser-heated gold nanoshells as the photothermal source in tissue-like phantoms. The photothermal OCT system will include a pre-existing Doppler OCT system and an amplitude-modulated near infrared (NIR) heating laser. Phantoms containing gold nanoshells that absorb in the NIR (the optical window where light penetrates deepest in tissue), polystyrene spheres as scatterers and hemoglobin as an absorber will be used to characterize the photothermal signal from gold nanoshells in a tissue-like environment. The second aim is to test the potential for Doppler OCT to measure changes in tumor microvascular flow rates in response to anti- angiogenic drugs in vivo in an animal model. Vascular endothelial growth factor (VEGF) is an angiogenic factor that is overexpressed in certain types of cancers. Bevacizumab is an anti-human VEGF antibody that induces tumor shrinkage in patients with solid tumors. Real time Doppler OCT (an existing technology) will be used to image flow rates in the microvessels of colon cancer tumors grown in dorsal skin flap mouse window chamber model before and at specific time points after bevacizumab treatment, and in control animals without bevacizumab treatment. The third and final aim of the proposed work is to test the potential for combined photothermal and Doppler OCT imaging of tumor microvascular VEGF levels and flow rates in response to anti-angiogenic drugs in vivo. Gold nanoshells, bioconjugated to antibodies against the VEGF receptor, will be intraveneously injected into the tumor vasculature of the mice. Photothermal and Doppler OCT will be used to image the amount and distribution of VEGF receptors, and microvessel flow rates, respectively, in control animals and in bevacizumab-treated animals before and at distinct time points after bevacizumab treatment. Relevance: The majority of cancer deaths are due to metastatic disease that fails to respond to chemotherapeutic drugs. This work could provide a minimally invasive method to monitor and study tumor response to cancer therapy in animal models. In the future, this technology could be used to provide individualized care to cancer patients, thus decreasing cancer morbidity and mortality.