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Dosimetry of 60/61/62/64Cu-ATSM: a hypoxia imaging agent for PET

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Abstract

Purpose

Cu-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) is an effective marker for the delineation of hypoxic tissue. Dosimetry calculations by the established Medical Internal Radionuclide Dose (MIRD) approach were performed with both animal and patient data.

Methods

Human absorbed dose estimates extrapolated from rat data were based on the biodistribution of 61Cu-ATSM in adult rats. Eighteen tissues were harvested and time–activity curves generated. The measured residence times and the MIRD S-values for 60Cu-ATSM were used to estimate human absorbed doses. The biodistribution of the tracer was directly measured in five patients injected with approximately 480 MBq of 60Cu-ATSM and imaged by positron emission tomography (PET) with a whole-body protocol. The combined data from all patients were used to derive organ residence times, and organ doses were calculated by MIRD methodology for 60Cu-ATSM, 61Cu-ATSM, 62Cu-ATSM, and 64Cu-ATSM.

Results

Human absorbed dose estimates extrapolated from rat biodistribution data indicated that the kidneys appeared to be the dose-limiting organ (0.083 mGy/MBq) with a whole-body dose of 0.009 mGy/MBq. Based on the human PET imaging data, the liver appeared as the dose-limiting organ, with an average radiation dose of 0.064 mGy/MBq. The whole-body dose was 0.009 mGy/MBq and the effective dose was 0.011 mSv/MBq.

Conclusion

These relatively small absorbed doses to normal organs allow for the safe injection of 500–800 MBq of 60Cu-ATSM, which is sufficient for PET imaging in clinical trials.

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Acknowledgements

We thank Margaret Morris and Elizabeth Conrad for their technical assistance with the animal studies. We thank Helen Kaemmerer, Jennifer Frye, and Linda Becker for their assistance with the clinical studies. We are very grateful to Dr. Barry Siegel for editing and for providing a critical review of the manuscript. We would also like to thank Michael Stabin for providing the 60Cu and 61Cu S-value tables as those were not calculated by the standard release of MIRDOSE 3.0.

This work was supported by a National Institute of Health grant (CA81525) and by a grant from the United States Department of Energy (DE-FG02-87ER60512). Production of Cu radionuclides was partially supported by NCI Grant No. R24 CA 86307. The authors are in full control of the data and therefore agree to allow EJNM to review the data if so requested by EJNM.

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Authors and Affiliations

  1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway, St. Louis, MO, 63110, USA

    Richard Laforest, Farrokh Dehdashti, Jason S. Lewis & Sally W. Schwarz

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  1. Richard Laforest
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  2. Farrokh Dehdashti
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  3. Jason S. Lewis
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Correspondence to Richard Laforest.

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Laforest, R., Dehdashti, F., Lewis, J.S. et al. Dosimetry of 60/61/62/64Cu-ATSM: a hypoxia imaging agent for PET. Eur J Nucl Med Mol Imaging 32, 764–770 (2005). https://doi.org/10.1007/s00259-004-1756-x

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  • DOI: https://doi.org/10.1007/s00259-004-1756-x

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