Targeted Dual Modality Imaging for Detection and Removal of Head and Neck Cancer

摘要 尽管手术技术不断进步，但原发肿瘤和淋巴结的术中方法 在过去的30年里，检测没有改变。为此，我们建议使用荧光和核 标记的抗EGFR抗体（帕尼单抗）用于原发性肿瘤的靶向双模态成像（TMRI） 在本申请中，我们提出 使用标记的帕尼单抗，因为它已经在几个早期阶段的研究中取得了成功，我们介绍了两个 用于术中检测非常小（1 mm 3）肿瘤沉积物的新概念。首先，我们将联合收割机 光学成像剂的高分辨率/深度受限成像性能 核武器的深度限制特性。其次，我们表明，这两个代理人可以系统地 施用用于检测肿瘤阳性淋巴结。我们提供广泛的临床数据， HNSCC，以证明使用抗EGFR可检测到尺寸小于1 mm 3的肿瘤碎片 抗体（帕尼单抗）作为靶向分子，以满足标题为“光学”的PAR-20-295的需要。 用于体内敏感癌症检测的荧光方法和技术。当使用抗EGFR 单独用于成像的抗体不是创新，应在PAR背景下考虑创新- 20-295，要求应用程序使用“......具有先前证明的 小肿瘤的检测”。为此，我们引入了双模态成像，并利用它 淋巴结分子成像本研究旨在符合FDA关于外科成像的指南 审判符合头颈癌切除术条件的患者将接受全身性给予抗肿瘤药物， 用IRDye 800（pan 800）或111铟（111 In-pan）标记的EGFR抗体（帕尼单抗）， 荧光信号和核信号。在全身施用两种药剂后，SPECT/CT将 以确定肿瘤阳性边缘和肿瘤阳性淋巴结的位置。的 然后，患者将接受原发肿瘤切除术和颈淋巴结清扫术， 引导，引导。我们假设，引入靶向双重 模态成像（TMRI）将改善术中决策。

Abstract Despite advances in operative technology, intraoperative methods for primary tumor and lymph node detection have not changed in the past 30 years. To this end, we propose to use a fluorescent and nuclear labeled anti-EGFR antibody (panitumumab) for targeted dual modality imaging (TDMI) of the primary tumor and lymph nodes in head and neck squamous cell carcinoma (HNSCC) In this application, we propose to use labeled panitumumab since it has been successful in several early-stage studies, we introduce two novel concepts for intraoperative detection of very small (1 mm3) tumor deposits. First, we combine the high-resolution/depth-limited imaging properties of optical imaging agents with the low-resolution/not depth-limited properties of nuclear agents. Second, we show that these two agents can be systemically administered for the detection of tumor-positive lymph nodes. We provide extensive clinical data in HNSCC to demonstrate that tumor fragments less than 1 mm3 in size can be detected using anti-EGFR antibody (panitumumab) as the targeting molecular to fulfill the needs of PAR-20-295 entitled, ‘Optical fluorescent methods and technologies for sensitive cancer detection in vivo’. While use of anti-EGFR antibodies for imaging alone is not innovative, innovation should be considered in the context of PAR- 20-295 which requires applications use “…probes with previously demonstrated capabilities for the detection of small tumors”. To this end, we introduce dual modality imaging and leveraging this for molecular imaging lymph nodes. This study is designed to meet FDA guidelines for a surgical imaging trials. Patients eligible for head and neck cancer resection will receive a systemic administration of an anti- EGFR antibody (panitumumab) labeled with either IRDye800 (pan800) or 111Indium (111In-pan) for fluorescent and nuclear signal, respectively. After systemic administration of both agents, a SPECT/CT will be performed to identify the location of tumor-positive margins and tumor-positive lymph nodes. The patient will then undergo resection of the primary tumor and neck dissection using fluorescent and gamma probe guidance (while maintaining the standard of care). We hypothesize that introduction of targeted dual modality imaging (TDMI) will improve intraoperative decision making.