Contrast enhanced spectroscopic detection of oral cancer

描述(申请人提供)：每年约有31,000名美国人罹患口腔癌。鳞状细胞癌占所有口腔恶性病变的95%口腔鳞状细胞癌是一种会导致 大约一半的患者在确诊后五年内患病。早些时候 强调诊断，因为这可以提高存活率，从50% 8%至80%左右。对比剂增强的诊断应用 荧光光谱学可能为早期、无创检测提供一种有效手段 和快速检测上皮肿瘤转化。我们的目标是 开发一种独特的光谱造影剂，可局部应用于 应用荧光成像技术早期发现上皮性肿瘤。潜在的 我们的目标是假设来自对比度增强的光谱信息 口腔病变的荧光成像可以作为一种可靠的方法 准确、早期、无创性地检测癌前病变和癌变 口腔内的病变。 这项修订后的提案将侧重于专题的开发和测试 新型稀土络合物造影剂在核磁共振成像中的应用 在恶性转化中诱导荧光染料的选择性积聚 用于早期发现病变的上皮组织。我们的预赛 工作表明：(1)光谱信息之间有很好的相关性 对比增强荧光观察和病变的病理状态 在发育的早期阶段，以及(2)口腔恶性肿瘤的能力 与良性病变相比，病变选择性地积累造影剂 病变或正常组织。 我们建议合成一种可以在该区域激发的新造影剂 3 10-330 nm，进行细胞和体内研究；(1)优化 安全染料的化学结构和光谱性质 实际应用，(2)更好地理解细胞和形态 观察到的癌前和癌前病变对染料选择性吸收的基础 以及(3)检验建议的诊断能力 与其他技术相比的对比度增强方法以及 一系列临床前动物研究的组织病理学发现。这个 从这项研究中获得的知识可能会导致开发一种简单的、 一种廉价的非侵入性诊断工具，用于检测和筛查 口腔癌在牙医办公室，指导活检和随访 耳鼻咽喉科医生和口腔外科医生的可疑口腔病变。

DESCRIPTION (Provided by Applicant): Each year about 31,000 Americans develop oral cancer. Squamous cell carcinoma accounts for 95 percent of all malignant oral lesions Oral squamous cell carcinoma is a condition that will kill approximately half of patients afflicted within five years of diagnosis. Early diagnosis is stressed, because this could increase the survival rate from 50 percent to about 80 percent. Contrast enhanced diagnostic applications of fluorescence spectroscopy may offer an effective means for early, non-invasive and rapid detection of epithelial neoplastic transformation. Our goal is to develop a unique spectroscopic contrast agent that can be applied topically for early detection of epithelial neoplasm using fluorescence imaging. Underlying our aims are the hypotheses that spectral information from contrast-enhanced fluorescence images of oral lesions can be used as a reliable approach toward accurate and early non-invasive detection of pre-malignant and malignant lesions in the oral cavity. This revised proposal will focus on the development and testing of topical application of newly developed Lanthanide Chelate-based contrast agent to induce selective accumulation of a fluorescing dye in malignant transformed epithelial tissue for the purpose of early lesion detection. Our preliminary work has shown: (1) promising correlation between the spectral information observed in contrast-enhanced fluorescence and pathological state of the lesion in the early stage of development, and (2) the ability of malignant oral lesions to selectively accumulate the contrast agent as compared to benign lesions or normal tissue. We propose to synthesize a new contrast agent that can be excited in the region of 3 10-330 nm and perform cellular and in vivo studies to; (1) optimize the chemical structure and spectroscopic properties of the dye for safe and practical applications, (2) better understand the cellular and morphological basis for the observed selective uptake of the dye by pre-malignant and malignant oral tissues, and (3) examine the diagnostic power of the proposed contrast enhanced approach as compared to other techniques as well as histopathlogical findings in a series of pre-clinical animal studies. The knowledge gained from this study may lead to the development of a simple, inexpensive and non-invasive diagnostic tool for detection and screening of oral cancer in a dentists office, guiding the biopsy and follow up of suspicious oral lesions by otolaryngologists and oral surgeons.