Quantitative endoscopic imaging and structured light delivery for controlled drug

描述（由申请人提供）：晚期卵巢癌是美国最致命的妇科恶性肿瘤。由于早期疾病通常没有症状，大多数卵巢癌病例直到疾病扩散到腹腔内的许多远处部位（称为微转移）后才被诊断出来。尽管手术、放疗和化疗都有所改善，但转移性疾病的5年生存率仅为43%。因此，一个主要的挑战是很难切除腹腔内的数十或数百个转移性肿瘤结节。在这里，我们提出了一个全新的基于卟啉-磷脂掺杂（PoPD）脂质体的药物控制释放系统，由近红外（NIR）光直接触发。荧光内镜可以利用荧光对比的高灵敏度和特异性以及内镜的高分辨率。光动力学诊断（PDD）涉及使用光敏剂（例如卟啉类化合物），这些光敏剂特异性地积聚在癌组织中，因为外源性荧光造影剂已被证明有希望检测恶性肿瘤。然而，活体组织中强烈的组织吸收和散射会扭曲原始荧光信号，使其混淆

DESCRIPTION (provided by applicant): Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Since the early stage disease is generally without symptoms, the majority of ovarian cancer cases are not diagnosed until after the disease has spread to numerous distant sites, known as micrometastases, in the abdominal cavity. Although improvements in surgery, radiation and chemotherapy, the five-year survival rate for the metastatic disease is only 43%. Thus, a major challenge relates to difficulties in removing the dozens or hundreds metastatic tumor nodules within the abdominal cavity. Here, we propose a fundamentally new controlled drug release system based on porphyrin-phospholipid doped (PoPD) liposomes, triggered directly by near infrared (NIR) light. Fluorescence endoscopy can utilize the high sensitivity and specificity of fluorescence contrast and high resolution of endoscopy. Photodynamic diagnosis (PDD) involves using photosensitizers (e.g. porphyrin-based compounds) that specifically accumulate in the cancerous tissue as exogenous fluorescent contrast has demonstrated promise for detecting malignancies. However, strong tissue absorption and scattering in living tissue distorts raw fluorescence signal, confounding the true fluorescence contrast. To address this issue, we propose a quantitative endoscopic approach by applying spatial frequency domain imaging to obtain absolute fluorescence concentration for enhanced visualization of micrometastases. We will develop a flexible fiber based dual-channel endoscopy system that allows both quantitative fluorescence imaging and adaptive beam-shaping for light-induced drug (PoPD) delivery to tumors of any size and shape. The system will be able to be inserted into the abdominal cavity with only a keyhole incision being made, which is already routinely done in the clinic. The system utilizes a highly sensitive CCD camera and spatial frequency modulation scheme with a digital micro-mirror device for quantitative fluorescence imaging of drug distribution, light-triggered drug release and adaptive light delivery for optimized treatment of micrometastases. We expect that our novel illumination and drug release strategy will provide versatile adjustment of light dose and shape with respect to spatial distribution of micrometastasis to achieve high doxorubicin deposition to destroy micrometastasis with minimal side effects to the surrounding tissues. This treatment will permit lower doxorubicin doses to be administered while simultaneously achieving more specific drug delivery in order to destroy the micrometastases and improve survival rates.