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

We assessed the validity of “perfusion-metabolism coupling” hypothesis in recurrent glioma with 13N-ammonia (13N-NH3) PET/CT and 18F-fluorodeoxyglucose (18F-FDG) PET/CT. 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 13N-NH3 PET/CT and 18F-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. Based on the reference standard, 27/56 patients had recurrence. 13N-NH3 PET/CT and 18F-FDG PET/CT were concordant in 55/56 patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 13N-NH3PET/CT were 77.8, 86.2, 84.0, 80.7, and 82.1 %, respectively, and for 18F-FDG PET/CT were 77.8, 89.7, 87.5, 81.2, and 83.9 %, respectively. There was excellent agreement between results of 13N-NH3 PET/CT and 18F-FDG PET/CT (ĸ = 0.964; P < 0.001). The performances of 13N-NH3 PET/CT and 18F-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 (ρ = 0.866, P < 0.001 for T/W; ρ = 0.918, P < 0.001 for T/G). A combination of 13N-NH3 PET/CT and 18F-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.