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.
ICMIC-3 will lead to better quality and length of life for cancer patients by tailoring Molecular Imaging to optimize individual patient management. Molecular Imaging will lead to a deeper understanding of the biology of how drugs affect transfer of growth signals in the tumor cell, leading to improved treatment regimens that avoid resistance resulting in an improved chance of remission and cure in prostate and thyroid cancer and melanoma.
|Rodina, Anna; Wang, Tai; Yan, Pengrong et al. (2016) The epichaperome is an integrated chaperome network that facilitates tumour survival. Nature 538:397-401|
|Lee, Sang-Gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar et al. (2016) Copper-64 labeled liposomes for imaging bone marrow. Nucl Med Biol 43:781-787|
|Demoin, Dustin Wayne; Shindo, Masahiro; Zhang, Hanwen et al. (2016) Synthesis and evaluation of an (18)F-labeled pyrimidine-pyridine amine for targeting CXCR4 receptors in gliomas. Nucl Med Biol 43:606-11|
|Arevalo-Perez, Julio; Paris, Manuel; Graham, Michael M et al. (2016) A Perspective of the Future of Nuclear Medicine Training and Certification. Semin Nucl Med 46:88-96|
|Cheal, Sarah M; Xu, Hong; Guo, Hong-Fen et al. (2016) Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity â¸â¶Y- or Â¹â·â·Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates. Eur J Nucl Med Mol Imaging 43:925-37|
|Wang, Xiuyan; RiviÃ¨re, Isabelle (2016) Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics 3:16015|
|Cherkassky, Leonid; Morello, Aurore; Villena-Vargas, Jonathan et al. (2016) Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest 126:3130-44|
|Kadota, Kyuichi; Sima, Camelia S; Arcila, Maria E et al. (2016) KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma. Am J Surg Pathol 40:1579-1590|
|Mayor, Marissa; Yang, Neng; Sterman, Daniel et al. (2016) Immunotherapy for non-small cell lung cancer: current concepts and clinical trials. Eur J Cardiothorac Surg 49:1324-33|
|Adusumilli, Prasad S (2016) Spread through alveolar spaces: An aerogenous invasion in pulmonary adenocarcinomas. J Thorac Cardiovasc Surg 152:73-4|
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