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(N⁴-methylthiosemicarbazone) (⁶⁰Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of ⁶⁰CU-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with ⁶⁰Cu-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 ⁶⁰Cu-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 ⁶⁰Cu-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 ≥3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with ⁶⁰Cu-ATSM uptake (r=0.04; P=0.9). ⁶⁰CU-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of 60Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.