Assessing tumor hypoxia in cervical cancer by PET with 60Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone).
Tumor hypoxia indicates a poor prognosis. This study was undertaken to confirm our prior pilot results showing that pretreatment tumor hypoxia demonstrated by PET with (60)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) is a biomarker of poor prognosis in patients with cervical cancer. Thirty-eight women with biopsy-proved cervical cancer underwent (60)Cu-ATSM PET before the initiation of radiotherapy and chemotherapy. (60)Cu-ATSM uptake was evaluated semiquantitatively as the tumor-to-muscle activity ratio (T/M). A log-rank test was used to determine the cutoff uptake value that was strongly predictive of prognosis. All patients also underwent clinical PET with (18)F-FDG before the institution of therapy. The PET results were correlated with clinical follow-up. Tumor (60)Cu-ATSM uptake was inversely related to progression-free survival and cause-specific survival (P = 0.006 and P = 0.04, respectively, as determined by the log-rank test). We found that a T/M threshold of 3.5 best discriminated patients likely to develop a recurrence from those unlikely to develop a recurrence; the 3-y progression-free survival of patients with normoxic tumors (as defined by T/M of < or = 3.5) was 71%, and that of patients with hypoxic tumors (T/M of > 3.5) was 28% (P = 0.01). Tumor (18)F-FDG uptake did not correlate with (60)Cu-ATSM uptake, and there was no significant difference in tumor (18)F-FDG uptake between patients with hypoxic tumors and those with normoxic tumors (P = 0.9). Pretherapy (60)Cu-ATSM PET provides clinically relevant information about tumor oxygenation that is predictive of outcome in patients with cervical cancer.
Dehdashti
Farrokh
F
Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110, USA. dehdashtif@mir.wustl.edu
Grigsby
Perry W
PW
Lewis
Jason S
JS
Laforest
Richard
R
Siegel
Barry A
BA
Welch
Michael J
MJ
D000328:Adult; D000368:Aged; D015687:Cell Hypoxia; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013882:Thiosemicarbazones / Q000493:pharmacokinetics*; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*
D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D010100:Oxygen