Perfusion-metabolism coupling in recurrent gliomas: a prospective validation study with 13N-ammonia and 18F-fluorodeoxyglucose PET/CT

Introduction We assessed the validity of " perfusion-metabolism coupling" hypothesis in recurrent glioma with N-13-ammonia (N-13-NH3) PET/CTand F-18-fluorodeoxyglucose ((18)FFDG) PET/CT. Methods Fifty-six consecutive patients (age, 38.8+/-12.1 years; 62.5 % males) with histologically proven and previously treated glioma presenting with clinical suspicion of recurrence were prospectively enrolled and evaluated with N-13-NH3 PET/CT and F-18-FDG PET/CT. PET/CT images were evaluated both qualitatively and semiquantitatively. Tumor to white matter uptake ratio (T/W) and tumor to gray matter uptake ratio (T/G) were calculated and analyzed for both the modalities. A combination of clinico-radiological follow-up, repeated imaging, and biopsy (when available) were considered as the reference standard. Results Based on the reference standard, 27/56 patients had recurrence. N-13-NH3 PET/CT and F-18-FDG PET/CT were concordant in 55/56 patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of N-13-NH3PET/CT were 77.8, 86.2, 84.0, 80.7, and 82.1 %, respectively, and for F-18-FDG PET/CT were 77.8, 89.7, 87.5, 81.2, and 83.9 %, respectively. There was excellent agreement between results of N-13-NH3 PET/CT and F-18-FDG PET/CT (.= 0.964; P< 0.001). The performances of N-13-NH3 PET/CT and F-18-FDG PET/CT were not significantly different between high-grade and low-grade glioma (P= 1.000). A strong positive correlation was noted between the uptake ratios derived on the two modalities (rho= 0.866, P< 0.001 for T/W;.= 0.918, P< 0.001 for T/G). Conclusion A combination of N-13-NH3 PET/CT and F-18-FDG PET/CT demonstrates that perfusion and metabolism are coupled in recurrent gliomas. These tracers target two different but interrelated aspects of the same pathologic process and can be used as surrogates for each other.