This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this project, we will test the value of [18F]EF5-PET imaging to detect reduction in tumor hypoxia, using two novel approaches, alone or in combination. Both approaches are based on the exclusive requirement of glucose as an energy source for hypoxic cells. We previously reported that inhibition of the transcription factor, HIF-1, blocks the synthesis of glycolytic enzymes, thereby preventing hypoxic tumor cells from using glucose. Chronic HIF-1 inhibition led to hypoxic cell necrosis. The second approach that we have recently discovered is based on the fact that solid tumors contain a mixture of oxygenated and hypoxic regions. Hypoxic tumor cells primarily use glucose for energy production by glycolysis and release lactate. In the presence of oxygen, certain tumors are able to import lactate via the monocarboxylate transporter MCT1, and oxidize it to recover ATP. In this setting, lactate is a preferred substrate to glucose in the respiration process. Inhibition of MCT1 delays tumor growth and increases their sensitivity for radiotherapy due to the switch-over of oxidative tumor cells from lactate oxidation to glucose catabolism. This switch leads to death of hypoxic cells from glucose starvation. In this study we will monitor the efficiency of selective hypoxic cell kill in solid tumors upon inhibition of lactate transport (MCT1) and HIF-1?, using the hypoxia imaging agent [18F]EF5 as a quantitative PET tracer of hypoxia. We will compare the [18F]EF5 PET signal with the immunohistochemical analysis of EF5 binding. The goal of this project is to establish the potential of PET imaging technique, in combination with hypoxia imaging agent [18F]EF5, to monitor the success of hypoxia cell kill therapy in a non invasive manner.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005959-21
Application #
8171602
Study Section
Special Emphasis Panel (ZRG1-SBIB-P (40))
Project Start
2010-07-01
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
21
Fiscal Year
2010
Total Cost
$5,460
Indirect Cost
Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Tang, Xinyan; Jing, Liufang; Richardson, William J et al. (2016) Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration. J Orthop Res 34:1316-26
Hodgkinson, Conrad P; Bareja, Akshay; Gomez, José A et al. (2016) Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology. Circ Res 118:95-107
Schmeckpeper, Jeffrey; Verma, Amanda; Yin, Lucy et al. (2015) Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol 85:215-25
Roos, Justus E; McAdams, Holman P; Kaushik, S Sivaram et al. (2015) Hyperpolarized Gas MR Imaging: Technique and Applications. Magn Reson Imaging Clin N Am 23:217-29
He, Mu; Robertson, Scott H; Kaushik, S Sivaram et al. (2015) Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI. Magn Reson Imaging 33:877-85
Huang, Lingling; Walter, Vonn; Hayes, D Neil et al. (2014) Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer. Clin Cancer Res 20:1566-75
Huang, Jing; Guo, Jian; Beigi, Farideh et al. (2014) HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection. J Mol Cell Cardiol 66:157-64
Yuan, Ying; Gilmore, John H; Geng, Xiujuan et al. (2014) FMEM: functional mixed effects modeling for the analysis of longitudinal white matter Tract data. Neuroimage 84:753-64
He, Mu; Kaushik, S Sivaram; Robertson, Scott H et al. (2014) Extending semiautomatic ventilation defect analysis for hyperpolarized (129)Xe ventilation MRI. Acad Radiol 21:1530-41
van Rhoon, Gerard C; Samaras, Theodoros; Yarmolenko, Pavel S et al. (2013) CEM43°C thermal dose thresholds: a potential guide for magnetic resonance radiofrequency exposure levels? Eur Radiol 23:2215-27

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