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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-SRLB-9 (M1))
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Menkens, Anne E
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Sloan-Kettering Institute for Cancer Research
New York
United States
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McDevitt, Michael R; Thorek, Daniel L J; Hashimoto, Takeshi et al. (2018) Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer. Nat Commun 9:1629
Dunphy, Mark P S; Harding, James J; Venneti, Sriram et al. (2018) In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine. Radiology 287:667-675
Serganova, Inna; Moroz, Ekaterina; Cohen, Ivan et al. (2017) Enhancement of PSMA-Directed CAR Adoptive Immunotherapy by PD-1/PD-L1 Blockade. Mol Ther Oncolytics 4:41-54
Graham, Nicholas A; Minasyan, Aspram; Lomova, Anastasia et al. (2017) Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Mol Syst Biol 13:914
Lu, Shaohua; Tan, Kay See; Kadota, Kyuichi et al. (2017) Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma. J Thorac Oncol 12:223-234
Pankov, Dmitry; Sjöström, Ludvig; Kalidindi, Teja et al. (2017) In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME). Oncotarget 8:65917-65931
Kim, Kwanghee; Zhang, Hanwen; La Rosa, Stephen et al. (2017) Bombesin Antagonist-Based Radiotherapy of Prostate Cancer Combined with WST-11 Vascular Targeted Photodynamic Therapy. Clin Cancer Res 23:3343-3351
Shrestha, Liza; Patel, Hardik J; Kang, Yanlong et al. (2017) Copper Mediated Coupling of 2-(Piperazine)-pyrimidine Iodides with Aryl Thiols using Cu(I)Thiophene-2-carboxylate. Tetrahedron Lett 58:4525-4531
Lee, Jason T; Zhang, Hanwen; Moroz, Maxim A et al. (2017) Comparative Analysis of Human Nucleoside Kinase-Based Reporter Systems for PET Imaging. Mol Imaging Biol 19:100-108
Weidenauer, Lorenz; Wang, Tai; Joshi, Suhasini et al. (2017) Proteomic interrogation of HSP90 and insights for medical research. Expert Rev Proteomics 14:1105-1117

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