Quantitative endoscopic imaging and structured light delivery for controlled drug

用于受控药物的定量内窥镜成像和结构光传输

• 批准号: 8772899
• 负责人: Ulas Sunar
• 金额: $ 18.69万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8772899
• 关键词: Abdominal Cavity; Address; Adverse effects; American; Biodistribution; Biological Availability; Cancer Etiology; Cancer Patient; Cancerous; Cause of Death; Clinic; Clinical; Contrast Sensitivity; Custom; Deposition; Development; Devices; Diagnosis; Disease; Distant; Dose; Doxorubicin; Drug Controls; Drug Delivery Systems; Endoscopy; Female; Fiber; Fluorescence; Frequencies; Goals; Greater sac of peritoneum; Gynecologic; Head; Image; Imagery; Kinetics; Life; Light; Lighting; Liposomal Doxorubicin; Liposomes; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Maps; Masks; Methods; Micrometastasis; Neoplasm Metastasis; Nodule; Operative Surgical Procedures; Outcome; Ovarian; Ovarian Carcinoma; Patients; Pharmaceutical Preparations; Phospholipids; Photosensitizing Agents; Physiological; Platinum; Play; Porphyrins; Primary Neoplasm; Radiation therapy; Radiosurgery; Recurrence; Resected; Resistance; Resolution; Role; Scheme; Sensitivity and Specificity; Shapes; Signal Transduction; Site; Spatial Distribution; Staging; Structure; Surgical incisions; Survival Rate; Symptoms; System; Therapeutic; Therapeutic Agents; Tissues; Translations; Tumor Debulking; United States; absorption; advanced disease; base; charge coupled device camera; chemotherapy; controlled release; digital; drug distribution; flexibility; fluorescence imaging; improved; in vivo; instrument; light treatment; minimally invasive; nanocarrier; new technology; novel; novel strategies; oncology; optical imaging; pre-clinical; public health relevance; tool; tumor

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.

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，因此大多数卵巢癌病例直到疾病扩散到腹腔中的许多远处部位（称为微转移）后才被诊断出来。尽管手术、放疗和化疗有所改善，但转移性疾病的五年生存率仅为 43%。因此，主要的挑战涉及去除腹腔内数十或数百个转移性肿瘤结节的困难。在这里，我们提出了一种基于卟啉磷脂掺杂（PoPD）脂质体的全新控释药物系统，由近红外（NIR）光直接触发。荧光内窥镜可以利用荧光对比的高灵敏度和特异性以及内窥镜的高分辨率。光动力诊断 (PDD) 涉及使用光敏剂（例如基于卟啉的化合物），这些光敏剂专门在癌组织中积累，因为外源荧光对比已被证明有望用于检测恶性肿瘤。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，从而混淆了 真实的荧光对比度。为了解决这个问题，我们提出了一种定量内窥镜方法，通过应用空间频域成像来获得绝对荧光浓度，以增强微转移的可视化。我们将开发一种基于柔性光纤的双通道内窥镜系统，该系统允许定量荧光成像和自适应光束整形，以将光诱导药物（PoPD）输送到任何大小和形状的肿瘤。该系统只需做一个锁孔切口就可以插入腹腔，这在诊所已经是常规做法。该系统利用高灵敏度的 CCD 相机和空间频率调制方案以及数字微镜装置，对药物分布、光触发药物释放和自适应光传输进行定量荧光成像，以优化微转移的治疗。我们期望我们的新颖的照明和药物释放策略将针对微转移的空间分布提供光剂量和形状的多功能调整，以实现高阿霉素沉积，从而破坏微转移，同时对周围组织的副作用最小。这种治疗将允许施用较低的阿霉素剂量，同时实现更特异性的药物递送，以破坏微转移并提高存活率。