Diagnostic Nodal Staging with Nuclear and NIR Molecular Optical Imaging

描述（由申请人提供）：主要项目将侧重于在贝勒医学院（Baylor College of Medicine）开发的成像剂和设备的翻译，并在Michael E. DeBakey退伍军人管理局医疗中心（MEDVAMC）以及本陶布总医院（BTGH）。用于核成像和荧光成像的双标记成像剂将在化学核心中的ESTA和LI-COR专业知识下生产;使用仪器和断层扫描任务特定项目中构建的近红外（NIR）荧光成像和断层扫描设备和编写的算法成像;并在使用临床前测试核心中生成的安全性和毒性数据开发的组合FDA申请后获得批准。最初，我们将翻译两种已建立的药物，其靶向（i）淋巴间隙内的癌细胞和（ii）作为乳腺癌和黑色素瘤患者中肿瘤恶性程度标志的基质淋巴结隔室的重组。来自成功验证其他候选显像剂的任务特定项目的结果将被输入到主要项目的基础设施中，以进行I期和I/II期研究，证明核医学中的淋巴结分期、淋巴结切除术的术中指导和准确的分子病理学。包括其他联盟成员的规定被“纳入”癌症淋巴结分期网络的基础设施。这个转化研究网络建立在十多年的发展基础上，（i）用于癌症靶向的NIR缀合物，（ii）用于深部组织中荧光时间依赖性测量的新型仪器，以及（iii）能够实现非接触成像和与核成像集成的创新算法

DESCRIPTION (provided by applicant): The primary project will focus upon translation of imaging agents and devices developed at The Baylor College of Medicine (BCM) and translated in Phase I studies at The Michael E. DeBakey Veterans Administration Medical Center (MEDVAMC) as well as at Ben Taub General Hospital (BTGH). Dual labeled imaging agents for nuclear and fluorescence imaging will be produced under the BCM and LI-COR expertise in the Chemistry Core; imaged with near-infrared (NIR) fluorescence imaging and tomography devices built and algorithms written in the Instrumentation and Tomography Task Specific Projects; and approved following combinational FDA applications developed with safety and toxicity data generated in the Preclinical Testing Core. Initially we will translate two established agents which target (i) cancer cells within the lymphatic space and (ii) the reorganization of the stromal lymph node compartment as a hallmark of tumor malignancy in both breast cancer and melanoma patients. The results from Task Specific Projects that successfully validate additional candidate imaging agents will then be fed into the infrastructure of the primary project to conduct Phase 1 and Phase I/I I studies demonstrating nodal staging in Nuclear Medicine, intraoperative guidance for lymph node removal, and accurate molecular pathology. Provisions for including other consortia members are "build into" the infrastructure of the network for nodal staging of cancer. This Network for Translational Research builds upon over a decade of development of (i) NIR conjugates for cancer targeting, (ii)novel instrumentation for time-dependent measurement of fluorescence in deep tissues, and (iii) innovative algorithms which enable non-contact imaging and integration with nuclear imaging