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，但针对原发肿瘤和淋巴结的术中方法 过去 30 年来，检测没有任何变化。为此，我们建议使用荧光和核 标记抗 EGFR 抗体（帕尼单抗）用于原发肿瘤的靶向双模态成像 (TDMI) 头颈鳞状细胞癌 (HNSCC) 中的淋巴结和淋巴结 在本申请中，我们建议 使用标记的帕尼单抗，因为它已在多项早期研究中取得成功，我们介绍两种 用于术中检测非常小的（1 mm3）肿瘤沉积物的新概念。首先，我们结合 光学显像剂的高分辨率/深度限制成像特性，低分辨率/非 核制剂的深度限制特性。其次，我们证明这两种药物可以系统地 用于检测肿瘤阳性淋巴结。我们提供广泛的临床数据 HNSCC 证明可以使用抗 EGFR 检测小于 1 mm3 的肿瘤碎片 抗体（帕尼单抗）作为靶向分子，以满足 PAR-20-295 的需求，标题为“光学 用于灵敏体内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并不是创新，应该在 PAR- 的背景下考虑创新 20-295 要求应用程序使用“……具有先前演示的功能的探针 小肿瘤的检测”。为此，我们引入双模态成像并利用它 分子成像淋巴结。本研究旨在满足 FDA 的手术成像指南 试验。符合头颈癌切除资格的患者将接受抗肿瘤药物的全身给药 用 IRDye800 (pan800) 或 111Indium (111In-pan) 标记的 EGFR 抗体（帕尼单抗） 分别是荧光信号和核信号。两种药物全身给药后，SPECT/CT 将 进行以确定肿瘤阳性边缘和肿瘤阳性淋巴结的位置。的 然后，患者将接受使用荧光和伽马射线的原发肿瘤切除术和颈部清扫术 探头指导（同时保持护理标准）。我们假设引入有针对性的双重 模态成像（TDMI）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.