多尺度光学光声功能成像在肿瘤早期诊断及化疗疗效监控中的应用研究

Cancer has become the primary death cause of mankind and Chinese residents. Early-stage tumor diagnosis would greatly improve recovery. At present, however, traditional medical imaging modalities are difficult to achieve an effective way for early detection of cancer and efficacy monitoring. Tumor metabolism is in rapid proliferation and usually exhibits lower oxygen saturation and higher oxygen consumption. Since acidity is strictly regulated by the tumor microenvironment, pH value deviation can be used as important tumor prognosis. Herein, we propose to design exogenous pH-sensitive optical probe SNARF-5F to conjugate gold nanostar and RGD targeting peptides for detecting tumor microenvironmental physiological parameters such as pH value, microvascular changes, oxygen saturation and metabolism. We also propose to apply in vivo fluorescence imaging for whole-body imaging, tumor localization and pharmakinetical distribution in various organs; hemispherical photoacoustic tomography to visualize blood vessels in tumor, quantify vascular density and diameter; high resolution photoacoustic microscopy to image subtle blood vessels, capillary growth change and even a single cell. This hybridized imaging platform can simultaneously monitor chemotherapeutic drugs inhibiting tumor blood vessel growth. Combined with exogenous probe complex, multiscale optical/photoacoustic functional imaging is expected to achieve early diagnosis and timely efficacy monitoring before tumor size change can be detected.

恶性肿瘤已成为全人类及我国居民的首要致死疾病。越早发现和干预肿瘤发展，治愈的机会也就越大。而目前的传统医学成像方法很难实现有效的肿瘤早期检测与疗效监控。肿瘤新陈代谢处于急速增殖状态，病变区域通常表现出较低血氧饱和度和过高氧消耗。由于体内酸碱度受微环境严格调制，pH值偏离可作为肿瘤重要预兆指标。申请人设计外源对pH敏感的光学探针SNARF-5F偶联金纳米星与靶向性多肽用来检测肿瘤微环境的酸碱度、血管微观变化、血氧饱和度与氧代谢量等功能生理参数。申请人提出活体荧光仪对全身成像，明确肿瘤位置与探针在各器官分布；半球构型的光声断层成像进行肿瘤供养血管密度、管径等统计分析；高分辨率光声显微镜则对细微结构、毛细血管生长变化甚至单个细胞进行评估成像。此联用影像平台可同时监控化疗药物抑制肿瘤血管的持续作用过程。结合复合分子探针的多尺度光学光声功能成像有望实现在肿瘤尺寸变化可测之前的早期检测与疗效及时监控。

恶性肿瘤已成为全人类及我国居民的首要致死疾病。越早发现和干预肿瘤发展，治愈的机会也就越大。而目前的传统医学成像方法很难实现有效的肿瘤早期检测与疗效监控。肿瘤新陈代谢处于急速增殖状态，病变区域通常表现出较低血氧饱和度和过高氧消耗。由于体内酸碱度受微环境严格调制，pH值偏离可作为肿瘤重要预兆指标。申请人设计外源对pH敏感的光学探针用来检测肿瘤微环境的酸碱度、血管微观变化、血氧饱和度与氧代谢量等功能生理参数。申请人并开展了活体荧光仪明确了肿瘤位置与探针在各器官分布；半球构型的光声断层成像进行肿瘤供养血管密度、管径等统计分析；高分辨率光声显微镜则对细微结构、毛细血管生长变化甚至单个细胞进行评估成像。此联用影像平台可同时监控化疗药物抑制肿瘤血管的持续作用过程。结合复合分子探针的多尺度光学光声功能成像开展了在肿瘤尺寸变化可测之前的早期检测与疗效及时监控。本研究也探明了化疗药物抑制肿瘤增生血管在影像上的表现形式与生物学作用过程，通过生物统计学结果优化化疗的治疗方案，提高主体癌症生存率。本研究结合生物组织特异性、高效增强肿瘤信息提取的功能分子，实现了从传统肿瘤尺寸评估技术的非特异性物理显像向特异、功能、精细成像的转变；实现了从传统技术的大体形态学检测向微观形态学、生物代谢和分子影像的转变。