Contrast enhanced spectroscopic detection of oral cancer

描述（由申请人提供）：每年约有31，000名美国人发展 口腔癌鳞状细胞癌占所有恶性肿瘤的95 口腔鳞状细胞癌是一种会杀死 大约一半的患者在诊断后五年内受到影响。早期 强调诊断，因为这可能会增加生存率从50 %到80%左右。造影剂增强诊断应用 荧光光谱法可以提供一种有效的手段， 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，可以局部应用于 使用荧光成像早期检测上皮肿瘤。底层 我们的目标是假设，从对比度增强的光谱信息 口腔病变的荧光图像可以作为一种可靠的方法， 准确、早期、无创地检测癌前病变和恶性病变 口腔内的病变。 这一修订后的提案将侧重于开发和测试专题 新开发的镧系螯合物基造影剂的应用 诱导荧光染料在恶性转化细胞中选择性积累 上皮组织，用于早期病变检测。我们的初步 工作表明：（1）光谱信息之间有很好的相关性 观察对比增强荧光和病变的病理状态 在发展的早期阶段，和（2）恶性口腔癌的能力， 与良性病变相比， 病变或正常组织。 我们建议合成一种新的造影剂，可以在该区域激发 并进行细胞和体内研究，以：（1）优化 染料的化学结构和光谱性质， （2）更好地理解细胞和形态学 观察到的癌前病变选择性摄取染料的基础， 恶性口腔组织，和（3）检查的诊断能力的建议 与其他技术相比， 在一系列临床前动物研究中的组织病理学发现。的 从该研究中获得的知识可能导致开发一种简单的， 用于检测和筛选 口腔癌在牙医办公室，指导活检和后续的 耳鼻喉科医生和口腔外科医生怀疑的口腔病变。

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.