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

摘要 尽管手术技术取得了进步，但手术中治疗原发肿瘤和淋巴结的方法 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子 标记的抗EGFR抗体(Panitumumab)用于原发肿瘤的靶向双模式成像(TDMI) 和淋巴结在头颈部鳞状细胞癌(HNSCC)中的应用，我们建议 使用标记的Panitumumab由于它在几个早期研究中取得了成功，我们介绍了两个 术中检测极小(1mm3)肿瘤沉积的新概念。首先，我们结合了 低分辨率/非分辨率光学成像剂的高分辨率/限深成像特性 核毒剂的深度受限特性。其次，我们证明了这两个代理可以系统地 用于检测肿瘤阳性的淋巴结。我们提供了大量的临床数据 HNSCC证明，使用抗EGFR可以检测到尺寸小于1mm3的肿瘤碎片 抗体(Panitumumab)作为靶向分子以满足PAR-20-295的需要 用于体内灵敏癌症检测的荧光方法和技术。在使用抗EGFR的同时 仅用于成像的抗体不是创新的，创新应该在PAR的背景下考虑- 20-295，要求应用程序使用“…具有先前演示的功能的探测器 小肿瘤的检测“。为此，我们引入了双模式成像，并利用这一点 分子成像的淋巴结。这项研究旨在满足fda的外科成像指南。 审判。有资格接受头颈部癌症切除的患者将接受系统的抗肿瘤药物治疗 用IRDye800(Pan800)或111In(111In-PAN)标记的EGFR抗体(Panitumab)用于 分别是荧光信号和核信号。在系统地给药后，SPECT/CT将 以确定肿瘤阳性边缘和肿瘤阳性淋巴结的位置。这个 患者随后将接受原发肿瘤的切除和使用荧光素和伽玛刀的颈淋巴清扫术。 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 模式成像(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.