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In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM

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Abstract

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis(N 4-methylthiosemicarbazone) (60Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of 60Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with 60Cu-ATSM before initiation of therapy. 60Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2–46 months). It was demonstrated that PET imaging with 60Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible 60Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for 60Cu-ATSM was significantly lower in responders (1.5±0.4) than in nonresponders (3.4±0.8) (P=0.002). However, the mean SUV for 60Cu-ATSM was not significantly different in responders (2.8±1.1) and nonresponders (3.5±1.0) (P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M ≥3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with 60Cu-ATSM uptake (r=0.04; P=0.9). 60Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of 60Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.

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Acknowledgements

This work was supported by NIH Grant CA81525 and DOE Grant DE-FG02-87ER60512.

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Authors and Affiliations

  1. Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, 510 South Kingshighway Boulevard, St. Louis, MO 63110, USA

    Farrokh Dehdashti, Mark A. Mintun, Richard Laforest & Barry A. Siegel

  2. Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri, USA

    Jason S. Lewis, Richard Laforest & Michael J. Welch

  3. Department of Radiation Oncology, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri, USA

    Jeffrey Bradley

  4. Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Ramaswamy Govindan

  5. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA

    Farrokh Dehdashti, Mark A. Mintun, Jason S. Lewis, Jeffrey Bradley, Ramaswamy Govindan, Michael J. Welch & Barry A. Siegel

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  1. Farrokh Dehdashti
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Correspondence to Farrokh Dehdashti.

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Dehdashti, F., Mintun, M.A., Lewis, J.S. et al. In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur J Nucl Med Mol Imaging 30, 844–850 (2003). https://doi.org/10.1007/s00259-003-1130-4

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  • DOI: https://doi.org/10.1007/s00259-003-1130-4

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