Image-Guided Photodynamic Therapy of Lung Cancer

描述(申请人提供)：该探索性/发展研究奖将为Nwogu博士和Pandey博士提供资金，用于在临床前动物模型中研究一种用于图像引导(PET/荧光)手术和光动力疗法(PDT)的新型“多功能试剂”。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，术中辅助性光动力疗法也将得以完成。此外，合并疾病而无法手术切除的患者可以接受可重复的有效治疗(PDT)。1)比较~(124)I-PS2和~(18)F-脱氧葡萄糖(FDG)在SCID小鼠原位肺癌模型中对肺癌和淋巴结转移的显像效果。2)比较PS2光动力疗法和异丙酚钠(Photofrin(R))光动力疗法对人NSCLC皮下移植瘤的治疗效果。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更大的动物原位肺癌模型(如狗或猪)中的治疗效果。在这种较大的动物模型中，对肺肿瘤及其结节引流盆的PDT将得到更好的改进。随后将进行第一阶段的人体临床试验。适用于这些患者的目标亚群包括那些可切除的原发非小细胞肺癌患者，他们正在接受手术切除大于3厘米或侵犯周围结构的病变，或任何临床上患有同侧胸部淋巴结疾病的患者。在切除原发肿瘤及其引流淋巴结后，对区域淋巴结盆和手术切缘进行局部治疗，可以立即以最低的发病率提供治疗，可以极大地减少疾病复发并提高长期存活率。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.