Molecular optical coherence tomography for monitoring cancer therapy

描述(由申请人提供)：项目摘要：建议工作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OCT和多普勒OCT联合应用具有较高的分辨率、化学特异度、血流成像能力和较高的穿透深度，是监测抗血管生成药物对血管反应的有力工具。这项工作的第一个目的是开发和验证一种光热OCT系统，该系统以激光加热的金纳米壳层作为组织模体的光热源。光热OCT系统将包括一个预先存在的多普勒OCT系统和一个幅度调制的近红外(NIR)加热激光器。包含吸收近红外(光在组织中最深处的光学窗口)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模体将被用来在类似组织的环境中表征来自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测量体内抗血管生成药物反应的肿瘤微血管流速变化的可能性。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血管内皮生长因子抗体，可导致实体瘤患者的肿瘤缩小。实时多普勒OCT(一项现有技术)将被用来成像在背侧皮瓣小鼠窗腔模型中生长的结肠癌肿瘤微血管中的血流速度，在贝伐单抗治疗前和治疗后的特定时间点，以及在没有贝伐单抗治疗的对照动物中。这项工作的第三个也是最后一个目标是测试光热和多普勒OCT联合成像对体内抗血管生成药物反应的肿瘤微血管VEGF水平和血流速度的可能性。与抗血管内皮生长因子受体抗体生物结合的金纳米壳将被静脉注射到小鼠的肿瘤血管中。在贝伐单抗治疗前和治疗后的不同时间点，将使用光热和多普勒OCT分别对对照组动物和贝伐单抗治疗动物的血管内皮生长因子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化疗药物无效的转移性疾病造成的。这项工作可以为在动物模型中监测和研究肿瘤对癌症治疗的反应提供一种微创方法。未来，这项技术可以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.