Diagnostic Nodal Staging with Nuclear and NIR Molecular Optical Imaging

主要项目将侧重于翻译贝勒医学院（BCM）开发的显像剂和设备，并在迈克尔·e·德贝基退伍军人管理医疗中心（MEDVAMC）和本·陶布综合医院（BTGH）的一期研究中进行翻译。化学核心的BCM和LI-COR专业知识将生产用于核和荧光成像的双标记显像剂；使用近红外（NIR）荧光成像和断层扫描设备进行成像，并在仪器和断层扫描任务特定项目中编写算法；并根据临床前测试核心生成的安全性和毒性数据，批准了FDA的联合申请。首先，我们将翻译两种已建立的药物，它们针对(i)淋巴间隙内的癌细胞和（ii）基质淋巴结室的重组，作为乳腺癌和黑色素瘤患者肿瘤恶性的标志。来自任务特定项目的结果将成功验证额外的候选显像剂，然后将被输入到主要项目的基础设施中，以进行1期和I/I期研究，展示核医学中的淋巴结分期、术中淋巴结切除指导和准确的分子病理学。包括其他联盟成员的规定被“构建”到癌症节点分期网络的基础设施中。

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 modalities.