Analyzing Serial Hypoxia Images from 18 FMISO-PET: Modeling Transient and Chronic Hypoxia

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 7 de noviembre del 2006

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Presenter: Kelin Wang, PhD
Presenter's Affiliation: Memorial Sloan-Kettering, New York, NY
Type of Session: Plenary

Background

  • Oxygen is an important mediator of radiation-induced DNA damage. Thus, tumor hypoxia impedes the ability of radiation to kill tumor cells.
  • Tumor hypoxia has been demonstrated by many groups using hypoxia markers such as misonidazole or 5-fluoro-etanidazole.
  • Tumor hypoxia is an important factor in the radiation response.
  • Several mechanisms of hypoxia have been proposed:
    • Growth of tumor cells located at a great distance from any blood vessel can lead to "chronic" hypoxia.
    • Variations in blood flow can lead to ?acute? or ?transient? hypoxia, even in well-vascularized regions of tumor.

Materials and Methods

  • In vivo tumor hypoxia can be measured in patients using a positron-emitting agent, in this case 18F-misonidazole and PET scanning.
    • GE Discovery LS PET/CT was performed 2.7 hr after injection.
  • 20 patients with tumors were imaged with 18F-misonidazole PET.
    • 2 pre-treatment scans were performed using a GE Discovery LS PET/CT scanner, 2.7 hr after injection.
    • Images were fused based on the CT scans performed at the same time to allow for voxel by voxel comparison
  • Due to the fact that the scans were separated by 2-3 days, it was assumed that any constant hypoxia was due to chronic hypoxia conditions. Any differences could therefore be attributable to transient hypoxia.

Results

Based on the mathematical models that partitioned chronic and transient hypoxia, it was determined that transient hypoxia represents a minimal component of tumor hypoxia, around 10% (in 5 patients, the component of transient hypoxia ranged from 3.2%, 7.6%, 5.6%, 8.4%, and 2.1%).

Author's Conclusions

  • This imaging and mathematical modeling method based on 18F- misonidazole -PET scanning and separated by 2-3 days can partition chronic and transient hypoxia.
  • Chronic hypoxia is the dominant component of tumor hypoxia over this period of time.

Clinical/Scientific Implications

  • Functional imaging can inform radiation treatment planning. Currently, 18 FDG -PET has used glucose uptake to define metabolically active regions of tumor.
  • New functional imaging techniques, such as 18F-misonidazole-PET can image hypoxia. However, basing radiotherapy plans on a static image of hypoxia may be misleading, as hypoxia can vary regionally and over time.
  • These studies need to be extended to more patients in different tumor types in order to help better define how to use functional imaging in the clinical setting.

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