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，因此直到疾病扩散到腹腔中的众多远处（称为微量年）的远处的卵巢癌病例。尽管手术，放射线和化学疗法的改善，但转移性疾病的五年存活率仅为43％。因此，一个重大挑战涉及去除腹腔内数十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）脂质体的根本新的受控药物释放系统，直接由近红外（NIR）光直接触发。荧光内窥镜检查可以利用荧光对比度的高灵敏度和特异性和内窥镜检查的高分辨率。光动力学诊断（PDD）涉及使用光敏剂（例如基于卟啉的化合物），这些光敏剂是在癌组织中特别积累的，因为外源性荧光对比已显示出对检测恶性肿瘤的希望。然而，活组织中强的组织吸收和散射会扭曲原始荧光信号，使其混淆 真正的荧光对比。为了解决这个问题，我们通过应用空间频域成像来获得一种定量的内窥镜方法，以获得绝对荧光浓度以增强微转移的可视化。我们将开发一个基于柔性的双通道内窥镜系统，该系统允许定量荧光成像和适应性光束成型，用于光诱导的药物（POPD）递送到任何大小和形状的肿瘤。该系统只能进行钥匙孔切口，可以将系统插入腹腔中，该切口已经在诊所中常规进行。该系统利用具有数字微型镜设备的高度敏感的CCD摄像头和空间频率调制方案，用于对药物分布，光触发药物释放和自适应光输送的定量荧光成像，以优化对微转移的处理。我们预计，我们的新型照明和药物释放策略将相对于微量含量的空间分布提供多功能的光剂量和形状，以实现高氧霉素沉积，从而破坏微量含量，对周围组织的副作用最小。这种治疗方法将允许降低阿霉素剂量，同时同时实现更具体的药物输送，以破坏微型转移并提高生存率。