In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis(N-4-methylthiosemicarbazone) (Cu-60-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of Cu-60-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with Cu-60-ATSM before initiation of therapy. 60Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with Cu-60-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible 60Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for 60Cu-ATSM was significantly lower in responders (1.5 +/- 0.4) than in nonresponders (3.4 +/- 0.8) (P = 0.002). However, the mean SUV for Cu-60-ATSM was not significantly different in responders (2.8 +/- 1.1) and nonresponders (3.5 +/- 1.0) (P = 0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M < 3.0 and all six nonresponders had a T/M greater than or equal to 3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P = 0.7) and did not correlate with Cu-60-ATSM uptake (r = 0.04; p = 0.9). Cu-60-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of Cu-60-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.