Diagnostic Nodal Staging with Nuclear and NIR Molecular Optical Imaging

主要项目将侧重于贝勒医学院(BCM)开发的成像剂和设备的翻译，并在Michael E.DeBakey退伍军人管理医疗中心(MEDVAMC)和本陶布综合医院(BTGH)的第一阶段研究中翻译。将在化学核心的BCM和Li-COR专业知识下生产用于核和荧光成像的双标记成像剂；利用仪器和层析任务特定项目中构建的近红外(NIR)荧光成像和层析成像设备和编写的算法进行成像；以及批准使用临床前测试核心中生成的安全性和毒性数据开发的FDA组合应用。首先，我们将翻译两种已确定的药物，它们针对(I)淋巴空间内的癌细胞和(Ii)作为乳腺癌和黑色素瘤患者肿瘤恶性标志的间质淋巴间隔室的重组。成功验证其他候选显像剂的特定任务项目的结果将被输入到主要项目的基础设施中，以进行第一阶段和第一阶段/第一阶段研究，展示核医学中的结节分期、术中淋巴结清除指导和准确的分子病理学。将其他联盟成员包括在内的规定被“纳入”癌症结节分期网络的基础设施。 这个转译研究网络建立在(I)用于癌症靶向的近红外共轭化合物、(Ii)用于测量深层组织中随时间变化的荧光的新型仪器以及(Iii)能够实现非接触式成像和与核成像模式集成的创新算法的十多年的开发基础上。

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.