Prognostic significance of hypoxic PET using ¹⁸F-FAZA and ⁶²Cu-ATSM in non-small-cell lung cancer

Objectives: Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). Patients and methods: Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: ¹⁸F-fluoroazomycin arabinoside (¹⁸F-FAZA) (n=45) and/or ⁶²Cu-diacetyl-bis (N4)-methylsemithiocarbazone (⁶²Cu-ATSM) (n=22). All received ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. Results: A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of ¹⁸F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs (¹⁸F-FAZA, p<0.01; ⁶²Cu-ATSM, p<0.04), but not with that of ¹⁸F-FDG. The patients with a higher accumulation had significantly poorer overall survival [¹⁸F-FAZA, HR (hazard ratio), 9.50, p<0.01; ⁶²Cu-ATSM, HR, 4.06, p<0.05] and progression free survival (¹⁸F-FAZA, HR, 5.28, p<0.01, ⁶²Cu-ATSM, HR, 2.72, p<0.05). Conclusion: Both ¹⁸F-FAZA and ⁶²Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.