Imaging Radiobiology Laboratory

Molecular Imaging of Cancer Biology

Orthotopic pancreatic tumor xenografts  Imaging models of lung cancer

The primary goal of the Imaging Radiobiology Laboratory is to apply novel molecular imaging methods towards the study of radiation and cancer biology. To this end, we have focused on both the development and implementation of preclinical and clinical molecular imaging methods capable of visualizing and quantifying tumor behavior, and the use of these methods in laboratory and clinical studies to elucidate tumor biology and to improve the treatment of human disease.

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.

We have recently observed using in vivo bioluminescence imaging (BLI) that radiation modulates the migration of breast cancer cells. This process involves the expression of radiation-inducible cytokines that serve as chemoattractants for circulating tumor cells (CTCs). This phenomenon has important implications for using radiotherapy to cure patients whose tumors have shed cells into the circulation. We are currently elucidating the molecular and cellular mechanism of this process and evaluating its significance in clinical radiotherapy. This effort has expanded our ability to visualize the metastatic process.

Current research projects in this area include:

  • Comparison of murine subcutaneous, orthotopic, and spontaneous models of cancer using hypoxia imaging
  • Identification and molecular imaging of novel hypoxia-regulated protein targets
  • Evaluation of hypoxia PET-directed radiotherapy strategies
  • Development of imaging probes targeting the receptor tyrosine kinase Axl
  • Study of tumor cell migration and metastasis, and the effects of radiation on this process

Recent publications:

Prediction of tumor response to single- and multi-fraction radiotherapy by pre-treatment EF5 imaging
Tumor radiation response and EF5

Induction of tumor cell migration by radiation in vitro (left) and in vivo (right)
Radiation-induced tumor cell migration

Bioluminescence imaging of changes in tumor oxygenation
BLI and O2

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