MSKCC Center for Molecular Imaging in Cancer

描述(由申请人提供)：这是在活体细胞和分子成像中心(ICMIC)PSO向纪念斯隆-凯特琳癌症中心(ICMIC-3)提供资金的第三份竞争性提案。ICMIC-3寻求继续ICMICs-1和-2的生产力，以推进癌症的分子成像(ML)。ICMICs-1和ICMICs-2导致了用于ML的新工具和癌症生物学新特征的发现，如125篇原始研究论文所述；包括开发5个新的基因表达成像(GEI)载体，10个新的放射性示踪剂，包括3个T细胞示踪剂；5个FDA IND和6个临床方案。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，应用于个别患者的护理和管理”。我们的研究计划包括4个研究项目(RP1成像T细胞靶向及其在人类癌症中的功能；RP2癌基因诱导的代谢变化；RP3成像癌蛋白靶向抑制剂对肿瘤生长和代谢的影响；RP4通过正电子发射断层扫描改进前列腺癌的抗雄激素治疗)；2个开发项目(DPS；DP-A标记HSP90抑制剂在多发性胶质母细胞瘤的活体脑成像；DP-B成像间皮瘤嵌合受体T细胞靶向)；以及3个专业资源(SRS；化学与放射化学、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：rp1：基于GEI靶向前列腺癌抗原PSMA的嵌合T细胞的GMP生产，用于人体成像(Ponomarev/Blasberg)；rp2：使用新型核磁共振/S和正电子发射计算机断层扫描技术进行多模式代谢成像(库彻)；rp3；抑制PI3K和ras/ERK信号转导通路在黑色素瘤和甲状腺癌中的生物学和临床益处的药理学解剖(罗森/桑托斯)；RP4：全基因组RNA图谱，通过使用新型前列腺癌小鼠模型和新型AR抑制药物(Mellinghoff/Sawyers/Larson)，发现M1雄激素受体靶向和糖酵解的分子决定因素；DP-A：为跨越胶质瘤血脑屏障的嘌呤类HSP90抑制剂开发真正的示踪剂(Chisis/Mellinghoff/Lewis)；以及DP-B：具有杀瘤和靶向间皮瘤活性的嵌合T细胞(Sadelain/Riviere)。总而言之，我们塑造了ICMIC-3，使其与标准杆09-157的目标紧密相连。

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.