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


CONCLUSIONS
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.
Laforest
Richard
R
Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway, St. Louis, MO 63110, USA. laforestr@wustl.edu
Dehdashti
Farrokh
F
Lewis
Jason S
JS
Schwarz
Sally W
SW
D000042:Absorption; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000000981:diagnostic imaging; D003300:Copper; D003301:Copper Radioisotopes; D005260:Female; D006801:Humans; D000860:Hypoxia; D008175:Lung Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D011874:Radiometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D003300:Copper