Imaging Core

成像核心的目标是为个别项目提供独特的体内监测能力 为了连续和实时跟踪遗传改变的T淋巴细胞的转运和定位，骨 骨髓来源的祖细胞、内皮细胞和肿瘤细胞。这将是 通过监测单模态和多模态报告基因的表达，使用光学 （生物发光和荧光）、放射性核素（PET、SPECT和定量放射自显影）， 磁共振（MRI和MRS）和CT成像。这些非侵入性成像技术 在Memorial Sloan Kettering Cancer Center（MSKCC）建立，用于小动物和患者成像 问题研究 我们提出了一个两步战略：首先，建立和验证我们的成像目标在实验 第二，将我们成像技术的某些方面转化为患者研究， 本申请中提出的项目的背景。我们建议开发和验证一些混合动力汽车， 报告基因，允许在小动物中进行多模态体内成像。两个融合报告基因， RFP-hRLuc和eGFP-FLuc已与逆转录病毒核心一起开发，它们正在进行初步的 测试和验证;其他计划用于开发和评估。第一个临床研究， 用自体EBV转化的B淋巴细胞致敏的供体T淋巴细胞的运输成像 细胞系（EBV BLCL）中，并用NIT载体（其编码表面受体 用于选择的LNGFR和用于非侵入性成像的报告基因（HSV 1胸苷激酶，HSV 1-tk）。 建议用于接受过继治疗的EBV淋巴瘤患者。给予的供体T 淋巴细胞将用[124 I]-FIAU（一种放射性标记的探针， 被HSV 1-TK磷酸化并被捕获在转导的细胞中）和PET成像。

The objective of the Imaging Core is to provide individual projects with unique in vivo monitoring capability for sequential and real-time tracking of the transit and localization of genetically altered T- lymphocytes, bone marrow-derived progenitor cells, endothelial cells and tumor cells by noninvasive imaging. This will be accomplished by monitoring the expression of single and multi-modality reporter genes, using optical (bioluminescence and fluorescence), radionuclide (PET, SPECT and quantitative autoradiography), magnetic resonance (MRI and MRS) and CT imaging. These non-invasive imaging techniques are well established at Memorial Sloan Kettering Cancer Center (MSKCC) for both small-animal and patient imaging studies. We propose a two-step strategy: first, to establish and validate our imaging objectives in experimental animals, and second, to translate selected aspects of our imaging technology to patient studies within the context of the projects proposed in this application. We propose to develop and validated a number of hybrid reporter genes that allow for multi-modality in vivo imaging in small animals. Two fusion reporter genes, RFP-hRLuc and eGFP-FLuc, have been developed with the Retroviral Core and they are undergoing initial testing and validation; others are planned for development and assessment. The first clinical studies to image the trafficking of donor T lymphocytes that have been sensitized with autologous EBV transformed Blymphocyte cell line (EBV BLCL) and transduced with the NIT vector (that encodes a surface receptor (LNGFR) for selection and a reporter gene (HSV1 thymidine kinase, HSV1-tk) for noninvasive imaging is proposed for patients undergoing adoptive treatment EBV lymphomas. The administered donor T lymphocytes will be noninvasively monitored with [124I]-FIAU (a radiolabeled probe that is selectively phosphorylated by HSV1-TK and trapped in transduced cells) and PET imaging.