Imaging Radiobiology Laboratory

Molecular Imaging of Tumor Hypoxia

Molecular Imaging of Tumor Hypoxia

Key personnel: Sandeep Apte, Marta Vilalta, Jessica Perez, Guoqiang Cui

The role of oxygen in tumor progression and response to therapy has been a topic of study for over 50 years. In the last 15 years, methods for non-invasively detecting and imaging regions of hypoxia within tumors have advanced to a stage where they may be employed both in the study of this phenomenon and in the development of hypoxia- directed therapeutic strategies. Our laboratory is involved in the evaluation of established hypoxia imaging methods in preclinical and clinical situations, development of novel hypoxia- and hypoxic signaling-specific imaging methods, and application of these techniques in studying cancer biology and devising improved treatments. In collaboration with the MIPS program, we have implemented radiochemical syntheses of the hypoxia PET agents fluoromisonidazole (FMISO), fluoroazomycin arabinoside (FAZA), and EF5. We have also engineered reporter gene approaches towards visualizing hypoxia and hypoxia-specific gene expression, and synthesized new imaging probes specific for hypoxia-induced proteins.

Current research projects in this area include:

  • Translation of EF5 for use in clinical radiotherapy patients
  • Investigation of murine subcutaneous, orthotopic, and spontaneous models of cancer using hypoxia imaging
  • Differentiation of reporter gene expression and oxygen-mediated signal changes
  • Identification and molecular imaging of novel hypoxia-regulated protein targets
  • Evaluation of hypoxia PET-directed radiotherapy strategies

Recent publications:

  • Graves EE, Giaccia AJ. Imaging Tumoral Hypoxia: Oxygen Concentrations and Beyond. Oncology 2007, 21:368-378.
  • Cecic I, Chan D, Sutphin P, Ray P, Gambhir SS, Giaccia A, Graves EE. Oxygen sensitivity of reporter genes: implications for preclinical imaging of tumor hypoxia. Molecular Imaging 2007, 6:219-228.
  • Bennewith KL, Huang X, Ham CM, Graves EE, Erler JT, Kambham N, Feazell J, Yang GP, Koong A, Giaccia AJ.  The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth.  Cancer Research 2009; 69:775-784.
  • Graves EE, Maity A, Le QT.  The tumor microenvironment in NSCLC.  Seminars in Radiation Oncology (in press).

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