MSKCC Center for Molecular Imaging in Cancer

描述（由申请人提供）： 对PAR-04-069的这一答复是一份更新申请，其基础是在MSKCC最初的ICMIC资助期间开始的工作。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。在上一个供资期成功的基础上，提出了两个重点领域：a）将开发人报告基因构建体并用于研究和更好地理解患者中过继性T细胞疗法中的T细胞相互作用和活化，（项目1和2），和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，尤其是在实体瘤中（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CD 4和CD 8亚型以及嵌合T细胞与对前列腺癌具有人工反应性的T细胞，将使用人源性报告基因（P1和P2）在人体中进行研究：Blasberg，项目1负责人; O 'Rielly，共同领导人），以及PET成像的生存，激活，并响应细胞因子刺激的遗传重定向前列腺特异性T细胞（V. Ponomarev，项目2的领导人; M。Sadelain，共同领导人）。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，以预测对一类重要的新型血管生成抑制剂的敏感性，并开发非侵入性标记物（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）的分子成像方法将使用雄激素受体、HER 2和热休克蛋白90的新型放射性配体研究治疗反应的生物学。用于将新型信号转导抑制剂的作用转化为临床的体内成像方法学的发展（N.罗森，项目3负责人; Solit，共同领导人）和去势抵抗性转移性前列腺癌的分子成像（S。Larson，Project 5 leader; 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，新的分子成像范例将用于解决肿瘤学中的重要临床问题。

DESCRIPTION (provided by applicant): 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.