An Imaging Comparison of 64Cu-ATSM and 60Cu-ATSM in Cancer of the Uterine Cervix
Jason S. Lewis 1*,
Richard Laforest 1,
Farrokh Dehdashti 2,
Perry W. Grigsby 3,
Michael J. Welch 1,
and
Barry A. Siegel 2
1 Division of Radiological Sciences, Mallinckrodt Institute of Radiology, St. Louis, Missouri; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri
2 Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri
3 Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
* To whom correspondence should be addressed. E-mail: lewisj2{at}mskcc.org.
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Abstract |
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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
