Image-Guided Photodynamic Therapy of Lung Cancer

描述（由申请人提供）：本探索性/发展性研究奖将为博士提供资金。Nwogu和Pandey将在临床前动物模型中研究一种用于图像引导（PET/荧光）手术和光动力治疗（PDT）的新型“多功能剂”。将其转化为临床将显著改变局部非小细胞肺癌的治疗模式，并改善患者的预后。隐匿性淋巴结疾病的检测将得到加强，术中辅助光动力治疗可以完成。此外，因合并症不能手术切除的患者可以接受可重复的有效治疗（PDT）。为了达到我们的影像学和治疗目的，本研究分为以下几个目的：1)比较124I-PS2和18f -氟脱氧葡萄糖（FDG）在SCID小鼠原位肺癌模型中对肺肿瘤和淋巴结转移的影像学效果。2)比较PS2和卟啉钠（Photofrin(R)）光动力治疗SCID小鼠皮下移植的人NSCLC异种移植物的效果。在完成该项目后，我们计划在更大的动物原位肺癌模型（如狗或猪）中研究这种新型多功能放射性同位素的治疗效果。在这种更大的动物模型中，肺肿瘤及其淋巴结引流盆的PDT将得到更好的细化。随后将进行I期人体临床试验。适用的目标亚群包括可切除的原发性非小细胞肺癌患者，这些患者正在接受手术切除大于3cm或侵犯周围结构的病变，或任何患有临床同侧胸淋巴结疾病的患者。在切除原发肿瘤及其引流淋巴结后立即对区域淋巴结盆和手术边缘进行局部治疗，其发病率最低，可显著减少疾病复发并提高长期生存率。这是一种新的治疗模式。

DESCRIPTION (provided by applicant): This Exploratory/Developmental Research Award will provide the funds for Drs. Nwogu and Pandey to study a novel "Multifunctional Agent" for image guided (PET/fluorescence) surgery and photodynamic therapy (PDT) in preclinical animal models. Translating this to the clinic will markedly change the treatment paradigm for locoregional non-small cell lung cancer and result in improved outcomes for patients. Detection of occult lymph node disease will be enhanced and intraoperative adjuvant photodynamic therapy can be accomplished. Additionally, patients whose comorbidities preclude surgical resection can have a repeatable, effective therapy (PDT). In order to achieve our imaging and therapeutic goals, this study is divided into following aims: 1) Compare the effectiveness of 124I-PS2 and 18F-Fluorodeoxyglucose (FDG) in imaging of lung tumors and lymph node metastases using an orthotopic lung cancer model in SCID mice. 2) Compare the effectiveness of photodynamic therapy using PS2 and Porfimer Sodium (Photofrin(R)) in human NSCLC xenografts established subcutaneously in SCID mice. On completion of the proposed project, we plan to study the therapeutic efficacy of this novel multifunctional radioisotope in a larger animal orthotopic lung cancer model such as dogs or pigs. PDT to both the lung tumor and its nodal drainage basin will be better refined in such larger animal models. This will be followed by phase I human clinical trials. The target subset of patients to whom this would be applicable include those with resectable primary NSCLC who are undergoing surgery to resect lesions that are larger than 3 cm or invading surrounding structures, or any patients with clinical ipsilateral thoracic lymph node disease. A local therapy to the regional lymph node basin and surgical margins that can be delivered with minimal morbidity immediately following resection of a primary tumor and its draining lymph nodes could dramatically reduce disease recurrence and improve long term survival. This is a novel therapeutic paradigm.