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

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.