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

Abstract

UNLABELLED: Tumor uptake of copper(II)-diacetyl-bis(N(4)-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 (60)Cu 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 (60)Cu-ATSM and (64)Cu-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 (60)Cu-ATSM and (64)Cu-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 (64)Cu-ATSM was better than that with (60)Cu-ATSM because of lower noise. In addition, we found that the pattern and magnitude of tumor uptake of (60)Cu-ATSM and (64)Cu-ATSM on studies separated by 1-9 d were similar. CONCLUSION: (64)Cu-ATSM appears to be a safe radiopharmaceutical that can be used to obtain high-quality images of tumor hypoxia in human cancers.