PT - JOURNAL ARTICLE AU - Jason S. Lewis AU - Richard Laforest AU - Farrokh Dehdashti AU - Perry W. Grigsby AU - Michael J. Welch AU - Barry A. Siegel TI - An Imaging Comparison of <sup>64</sup>Cu-ATSM and <sup>60</sup>Cu-ATSM in Cancer of the Uterine Cervix AID - 10.2967/jnumed.108.051326 DP - 2008 Jul 01 TA - Journal of Nuclear Medicine PG - 1177--1182 VI - 49 IP - 7 4099 - http://jnm.snmjournals.org/content/49/7/1177.short 4100 - http://jnm.snmjournals.org/content/49/7/1177.full SO - J Nucl Med2008 Jul 01; 49 AB - 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.