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[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression

European Journal of Nuclear Medicine and Molecular Imaging volume 30, pages 695–704 (2003)Cite this article

Abstract

Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [18F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio (≥1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09–0.79) pretreatment and 0.32 (range −0.46–0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship between the hypoxic volume and the tumor volume or VEGF expression. Identification of hypoxia and development of a more complete biologic profile of STS will serve to guide more rational, individualized cancer treatment approaches.

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Acknowledgements

The authors wish to acknowledge the valuable help and useful suggestions provided by Mr. Mark Muzi, Research Scientist in the Department of Radiology regarding analysis of the data.

This research was supported by NIH grants CA-42045, CA-34570, and CA-65537

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Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, University of Washington Medical Center, Box 356113, Seattle, WA 98195, USA

    J. G. Rajendran, L. M. Peterson, J. R. Grierson, J. F. Eary & K. A. Krohn

  2. Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington, USA

    J. S. Rasey, L. K. Chin, P. D. Hofstrand & K. A. Krohn

  3. Department of Orthopedic Surgery, University of Washington Medical Center, Seattle, Washington, USA

    E. U. Conrad & J. D. Bruckner

  4. Radiation Oncology, British Columbia Cancer Control Agency, Vancouver, BC, Canada

    D. C. Wilson

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  1. J. G. Rajendran
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Correspondence to J. G. Rajendran.

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Rajendran, J.G., Wilson, D.C., Conrad, E.U. et al. [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression. Eur J Nucl Med Mol Imaging 30, 695–704 (2003). https://doi.org/10.1007/s00259-002-1096-7

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  • DOI: https://doi.org/10.1007/s00259-002-1096-7

Keywords

  • Soft tissue sarcomas
  • Hypoxia
  • FMISO
  • FDG
  • VEGF