Molecular optical coherence tomography for monitoring cancer therapy

描述（由申请人提供）：项目摘要：拟定工作的目的是开发一种新型分子成像技术，光热光学相干断层扫描（光热OCT），并将该技术与现有OCT技术（多普勒OCT）一起沿着用于监测癌症治疗。由于其高分辨率、化学特异性、血流成像能力和相对较高的穿透深度，光热和多普勒OCT组合将成为监测血管对抗血管生成药物的反应的有力工具。本研究的第一个目的是开发并验证一种以激光加热金纳米壳为光热源的光热OCT系统。光热OCT系统将包括一个预先存在的多普勒OCT系统和一个调幅近红外（NIR）加热激光器。含有在NIR（光穿透组织最深处的光学窗口）中吸收的金纳米壳、作为散射体的聚苯乙烯球和作为吸收体的血红蛋白的纳米粒子将用于表征来自组织样环境中的金纳米壳的光热信号。第二个目的是在动物模型中测试多普勒OCT测量肿瘤微血管流速响应于体内抗血管生成药物的变化的潜力。血管内皮生长因子（VEGF）是在某些类型的癌症中过表达的血管生成因子。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。将使用真实的时间多普勒OCT（现有技术）对贝伐珠单抗治疗前和治疗后特定时间点以及未接受贝伐珠单抗治疗的对照动物中背部皮瓣小鼠窗室模型中生长的结肠癌肿瘤微血管中的流速进行成像。拟议工作的第三个也是最后一个目的是测试结合光热和多普勒OCT成像的肿瘤微血管VEGF水平和流速在体内抗血管生成药物的反应的潜力。将与针对VEGF受体的抗体生物缀合的金纳米壳静脉内注射到小鼠的肿瘤脉管系统中。在对照动物和贝伐珠单抗给药动物中，在贝伐珠单抗给药前和给药后不同时间点，将分别使用光热和多普勒OCT对VEGF受体的数量和分布以及微血管流速进行成像。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。这项工作可以提供一种微创方法来监测和研究动物模型中肿瘤对癌症治疗的反应。在未来，这项技术可用于为癌症患者提供个性化护理，从而降低癌症发病率和死亡率。

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.