Application of 62Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET Imaging to Predict Highly Malignant Tumor Grades and Hypoxia-Inducible Factor-1α Expression in Patients with Glioma

BACKGROUND AND PURPOSE: Hypoxic tissue evaluation in glioma is important for predicting treatment response and establishing antihypoxia therapy. In this preliminary study, Cu-62-ATSM PET was used to determine its validity as a biomarker for distinguishing tumor grade and tissue hypoxia. MATERIALS AND METHODS: 6(2)Cu-ATSM PET was performed in 22 patients with glioma, and the Cu-62-ATSM SUVmax and T/B ratio were semiquantitatively evaluated. Cu-62-ATSM uptake distribution was qualitatively evaluated and compared with MR imaging findings. HIF-1 alpha expression, a hypoxia marker, was compared with Cu-62-ATSM uptake values. RESULTS: The Cu-62-ATSM SUVmax and T/B ratio were significantly higher in grade IV than in grade III gliomas (P = .014 and .018, respectively), whereas no significant differences were found between grade III and grade II gliomas. At a T/B ratio cutoff threshold of 1.8, Cu-62-ATSM uptake was predictive of HIF-1 alpha expression, with 92.3% sensitivity and 88.9% specificity. The mean T/B ratio was also significantly higher in HIF-1 alpha-positive glioma tissue than in HIF-1 alpha-negative tissue (P = .001). Using this optimal threshold of T/B ratio, Cu-62-ATSM PET showed regional uptake in 61.9% (13/21) of tumors within the contrast-enhanced region on MR imaging, which was significantly correlated with presence of a necrotic component (P = .002). CONCLUSIONS: Our results demonstrated that Cu-62-ATSM uptake is relatively high in grade IV gliomas and correlates with the MR imaging findings of necrosis. Moreover, the Cu-62-ATSM T/B ratio showed significant correlation with HIF-1 alpha expression. Thus, Cu-62-ATSM appears to be a suitable biomarker for predicting highly malignant grades and tissue hypoxia in patients with glioma.