MSKCC Center for Molecular Imaging in Cancer

对PAR-04-069的响应是基于ICMIC在MSKCC最初资助期间开始的工作的更新申请。这项新应用的中心主题是将我们所取得的进展转化为肿瘤学的临床研究和应用。基于过去资助期的成功，提出了两个重点领域：a)人类报告基因构建将被开发并用于研究和更好地理解患者过继T细胞治疗中的T细胞相互作用和激活（项目1和2），以及b)与评估药物治疗反应相关的关键分子的分子成像，特别是对于信号转导抑制剂，特别是在实体肿瘤中（项目3-5）。报告基因成像在过继细胞治疗中的应用，包括靶向CD4和CD8亚型以及对前列腺癌具有人工反应性的T细胞嵌合T细胞，将使用人类来源的报告基因（P1和P2）在人体内进行研究：成像T细胞相互作用在ebv相关淋巴瘤过继治疗中的应用(R. Blasberg，项目1负责人；R. O'Rielly，共同领导)，以及基因重定向前列腺特异性T细胞的存活、激活和对细胞因子刺激的反应的PET成像（V. Ponomarev，项目2负责人；M. Sadelain，共同领导）。在项目3中，高场MRI/MRS将探测体内药物转化和代谢的药效学，预测对一类重要的新血管生成抑制剂的敏感性，并开发非侵入性标志物（J. Koutcher，项目3负责人）。在项目4和5中，基于正电子发射断层扫描（PET）的分子成像方法将研究治疗反应的生物学，使用雄激素受体、HER2和热休克蛋白90的新型放射配体。新型信号转导抑制剂的体内成像方法的发展，以转化为临床（N. Rosen，项目3负责人；D. Solit，联合负责人），以及去势抵抗性转移性前列腺癌的分子成像（S. Larson，项目5负责人；H. Scher和P. Smith-Jones，共同负责人）。转化发展项目，基于肿瘤学的职业发展，分子生物学，放射化学/回旋加速器和数据分析研究资源提供了必要的基础设施。总之，新的分子成像范式将用于解决肿瘤学中重要的临床问题。

This response to PAR-04-069 is a renewal application based on work begun during the original period of ICMIC funding at MSKCC. The central theme of this new application is translation of the progress we have made into clinical research and application in oncology. Two focus areas are proposed which build on the success of the past funding period: a) human reporter gene constructs will be developed and used to study and better understand T cell interactions and activation in adoptive T cell therapy in patients, (Projects 1 and 2), and b) molecular imaging of the key molecules relevant to assessing drug treatment response, particularly for signal transduction inhibitors, and especially in solid tumors (Projects 3-5). Reporter gene imaging applications in adoptive cell therapy, including targeting of CD4 and CD8 sub-types and chimeric T-cells with T-cells with artificial reactivity to prostate cancer, will be studied in man using human derived reporter genes (P1 and P2): Imaging T cell interactions in adoptive therapy of EBV-associated lymphoma (R. Blasberg, Project 1 leader; R. O'Rielly, co-leader), and PET imaging of survival, activation, and response to cytokine stimulation of genetically retargeted prostate specific T cells (V. Ponomarev, Project 2 leader; M. Sadelain, co-leader). In Project 3, high field MRI/MRS will probe the pharmacodynamics of in vivo drug conversion and metabolism, to predict sensitivity for an important new class of angiogenesis inhibitors, and to develop of non-invasive markers (J. Koutcher, Project 3 leader). In Projects 4 and 5, Positron Emission Tomography (PET) based molecular imaging methods will study the biology of treatment response, using novel radioligands for androgen receptor, HER2, and heat shock protein 90. The development of methodologies for the in vivo imaging of the effects of novel inhibitors of signal transduction for translation to the clinic (N. Rosen, Project 3 leader; D. Solit, co-leader), and molecular imaging of castrate-resistant metastatic prostate cancer (S. Larson, Project 5 leader; H. Scher and P. Smith-Jones, co leaders). Translational developmental projects, oncology based career development, and molecular biology, radiochemistry/cyclotron and data analysis research resources provide essential infrastructure. In summary, novel molecular imaging paradigms will be used to address important clinical questions in oncology.