MSKCC Center for Molecular Imaging in Cancer

描述（由申请人提供）：这是纪念斯隆-凯特琳癌症中心（ICMIC-3）为体内细胞和分子成像中心（ICMIC）PSO资助提交的第三份竞争提案。ICMIC-3旨在继续ICMIC-1和ICMIC-2的生产力，以推进癌症中的分子成像（MI）。ICMIC-1和ICMIC-2导致了用于MI的新工具和癌症生物学的新特征的发现，如125篇原始研究论文中所述;包括开发5种新的基因表达成像（GEI）载体、10种新的放射性示踪剂，包括3种T细胞示踪剂; 5种FDA IND和6种临床方案。我们对ICMIC-3的愿景是“癌症生物学与实时、非侵入性成像相结合，用于个体患者护理和管理”。我们的研究计划包括4个研究项目（RP：RP 1成像T细胞靶向和功能在人类癌症; RP 2癌基因诱导的代谢变化; RP 3成像癌蛋白靶向抑制剂对肿瘤生长和代谢的影响; RP 4通过正电子发射断层扫描改善抗雄激素治疗前列腺癌）; 2个开发项目（DP; DP-A用于小动物多形性胶质母细胞瘤体内脑成像的HSP 90抑制剂的放射性标记; DP-B成像间皮瘤中的间皮素嵌合受体T细胞靶向）;和3个专业资源（SR;化学和放射化学，基因转移和定量成像）。ICMIC-3研究计划利用了最具创新性和临床相关性的先前发现/开发，包括：RP 1：基于GEI，针对前列腺癌抗原PSMA的嵌合T细胞的GMP生产，用于人体成像（Ponomarev/Blasberg）; RP 2：采用新型MRI/S和PET技术的多模态代谢组学成像（Koutcher）; RP 3;对黑色素瘤和甲状腺癌中抑制PI 3 K和Ras/ERK信号转导通路的生物学和临床益处的药理学分析（罗森/桑托斯）; RP 4：全基因组RNA分析用于发现Ml雄激素受体靶向和糖酵解的分子决定因素，通过使用新的前列腺癌小鼠模型，和新的AR抑制剂药物（Mellinghoff/Sawyers/Larson）; DP-A：开发基于嘌呤的HSP 90抑制剂的真正示踪剂，其在神经胶质瘤中穿过血脑屏障（Chiosis/Mellinghoff/刘易斯）;和DP-B：具有杀肿瘤和对间皮瘤中的间皮素具有靶向性质的嵌合T细胞（Sadelain/里维埃）。总而言之，我们已经使ICMIC-3紧密遵循PAR 09-157的目标。

DESCRIPTION (provided by applicant): This is the third competing proposal submitted for In Vivo Cellular and Molecular Imaging Center (ICMIC) PSO funding from Memorial Sloan-Kettering Cancer Center (ICMIC-3). ICMIC-3 seeks to continue the productivity of ICMICs-1 and-2 for advancing Molecular Imaging (Ml) in cancer. ICMICs-1 and -2 led to new tools for Ml and the discovery of novel features of cancer biology, as described in 125 original research papers; including development of 5 novel gene expression imaging (GEI) vectors, 10 new radiotracers, including 3 T-cell tracers; 5 FDA IND's and 6 clinical protocols. Our vision for ICMIC-3 is "cancer biology integrated with real-time, noninvasive imaging for application in individual patient care and management". Our research plan includes 4 Research Projects (RP's: RP1 Imaging T-cell Targeting and Function in Human Cancer; RP2 Oncogene Induced Changes in Metabolism; RP3 Imaging the Effects of Oncoprotein-Targeted Inhibitors on Tumor Growth and Metabolism; and RP4 Refining Antiandrogen Therapy for Prostate Cancer through Positron-Emission-Tomography); 2 Developmental Projects (DPs; DP-A Radiolabeling of HSP90 Inhibitors for Small Animal In Vivo Brain Imaging of Glioblastoma Multiforme; DP-B Imaging mesothelin chimeric receptor T-cell targeting in mesothelioma); and, 3 Specialized Resources (SRs; Chemistry & Radiochemistry, Gene Transfer and Quantitative Imaging). The ICMIC-3 research plan leverages the most innovative and clinically relevant prior discoveries/ developments and includes: RP1: GMP production of chimeric T-cells which target PSMA, an antigen in prostate cancer, based on GEI, for imaging in man (Ponomarev/Blasberg); RP2: multimodality metabolomic imaging with novel MRI/S and PET technology (Koutcher); RP3; pharmacologic dissection of the biology and clinical benefit of inhibiting the PI3K and Ras/ERK signal transduction pathways in melanoma and thyroid cancer (Rosen/Santos); RP4: genome wide RNA profiling for discovery of molecular determines of Ml androgen receptor targeting and glycolysis, through the use of novel mouse models of prostate cancer, and novel AR inhibitor drugs (Mellinghoff/Sawyers/Larson); DP-A: development of true tracers for Purine-based HSP90 inhibitors which cross blood brain barrier in glioma (Chiosis/Mellinghoff/Lewis); and DP-B: Chimeric T-cells with tumoricidal and targeting properties for mesothelin in mesothelioma (Sadelain/Riviere). In summary, we have shaped ICMIC-3 to closely adhere to the goals of PAR 09-157.