Image-Guided Photodynamic Therapy of Lung Cancer

描述（由申请人提供）：该探索/发展研究奖将为Nwogu和Pandey博士提供资金，用于在临床前动物模型中研究用于图像引导（PET/荧光）手术和光动力学治疗（PDT）的新型“多功能药物”。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，合并症排除手术切除的患者可以有一个可重复的，有效的治疗（PDT）。为了达到我们的成像和治疗目标，本研究分为以下几个方面：1）利用SCID小鼠原位肺癌模型，比较124 I-PS2和18F-FDG在肺肿瘤和淋巴结转移成像中的有效性。2)比较使用PS2和Porfimer Sodium（Photofrin（R））的光动力疗法在SCID小鼠皮下建立的人NSCLC异种移植物中的有效性。在拟议的项目完成后，我们计划研究这种新型多功能放射性同位素在较大动物原位肺癌模型（如狗或猪）中的治疗效果。在这种较大的动物模型中，对肺肿瘤及其淋巴结流域的PDT将得到更好的改进。随后将进行I期人体临床试验。适用的目标患者亚组包括正在接受手术切除大于3 cm或侵犯周围结构的病变的可切除原发性NSCLC患者，或任何临床同侧胸淋巴结疾病患者。在切除原发性肿瘤及其引流淋巴结后立即对区域淋巴结盆和手术切缘进行局部治疗，发病率最低，可显著降低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.