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First published online June 13, 2008, 10.2967/jnumed.108.051326
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Journal of Nuclear Medicine Vol. 49 No. 7 1177-1182
© 2008 by Society of Nuclear Medicine
doi: 10.2967/jnumed.108.051326

Basic Science Investigation

An Imaging Comparison of 64Cu-ATSM and 60Cu-ATSM in Cancer of the Uterine Cervix

Jason S. Lewis1,2, Richard Laforest1,2, Farrokh Dehdashti2,3, Perry W. Grigsby2,4, Michael J. Welch1,2 and Barry A. Siegel2,3

1 Division of Radiological Sciences, Mallinckrodt Institute of Radiology, St. Louis, Missouri; 2 Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; 3 Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri; and 4 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri

Correspondence: For correspondence or reprints contact: Jason S. Lewis, Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10065. E-mail: lewisj2{at}mskcc.org

Tumor uptake of copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (copper-ATSM), a hypoxia-targeting radiopharmaceutical, assessed by PET has been found to correlate with prognosis in several human cancers. Wide clinical utility of this tracer will require its labeling with a copper radionuclide having a longer half-life than the 60Cu used in studies to date. The purpose of this work was to obtain the requisite preclinical data for copper-ATSM to file an investigational new drug application, followed by a crossover comparison of PET image quality and tumor uptake with 60Cu-ATSM and 64Cu-ATSM in women with cancer of the uterine cervix. Methods: The preclinical toxicology and pharmacology of a copper-ATSM formulation was examined using standard in vitro and in vivo assays, as well as 14-d toxicity studies in both rats and rabbits. For the clinical test–retest imaging study, 10 patients with cervical carcinoma underwent PET on separate days with 60Cu-ATSM and 64Cu-ATSM. Image quality was assessed qualitatively, and the tumor-to-muscle activity ratio was measured for each tracer. Results: The toxicology and pharmacology data demonstrated that the formulation has an appropriate margin of safety for clinical use. In the patient study, we found that the image quality with 64Cu-ATSM was better than that with 60Cu-ATSM because of lower noise. In addition, we found that the pattern and magnitude of tumor uptake of 60Cu-ATSM and 64Cu-ATSM on studies separated by 1–9 d were similar. Conclusion: 64Cu-ATSM appears to be a safe radiopharmaceutical that can be used to obtain high-quality images of tumor hypoxia in human cancers.

Key Words: Cu-ATSM • hypoxia • 60Cu • 64Cu • cervical cancer

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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