The aim of this study was to determine the spatial correlation of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) uptake and the concentrations of choline (Cho), creatine (Cr), and total N-acetylaspartate (tNAA) determined with proton magnetic resonance spectroscopic imaging ((1)H MRSI) in cerebral gliomas for the multimodal evaluation of metabolic changes.
Methods: (18)F-FET PET and 2-dimensional (1)H MRSI were performed in 15 patients with cerebral gliomas of World Health Organization (WHO) grades II-IV. PET and (1)H MRSI datasets were coregistered by use of mutual information. On the basis of their levels of (18)F-FET uptake, 4 different areas in a tumor (maximum, strong, moderate, and low (18)F-FET uptake) were defined on PET slices as being congruent with the volume of interest in the (1)H MRSI experiment. (18)F-FET uptake in lesions was evaluated as tumor-to-brain ratios. Metabolite concentrations for Cho, Cr, and tNAA and Cho/tNAA ratios were computed for these 4 areas in the tumor and for the contralateral normal brain.
Results: In the area with maximum (18)F-FET uptake, the concentration of tNAA (R= -0.588) and the Cho/tNAA ratio (R=0.945) correlated significantly with (18)F-FET uptake. In the areas with strong and moderate (18)F-FET uptake, only the Cho/tNAA ratios (R=0.811 and R=0.531, respectively) were significantly associated with amino acid transport. At low (18)F-FET uptake, analysis of the correlations of amino acid uptake and metabolite concentrations yielded a significant result only for the concentration of Cr (R=0.626). No correlation was found for metabolite concentrations determined with (1)H MRSI and (18)F-FET uptake in normal brain tissue. Maximum (18)F-FET uptake and the tNAA concentration were significantly different between gliomas of WHO grades II and IV, with P values of 0.032 and 0.016, respectively.
Conclusion: High (18)F-FET uptake, which is indicative of tumor cell infiltration, associates with neuronal cell loss (tNAA) and changes in ratios between parameters representing membrane proliferation and those of neuronal loss (Cho/tNAA ratio), which can be measured by (1)H MRSI. The significant correlation coefficients detected for Cr in regions with low (18)F-FET uptake suggests an association between the mechanism governing amino acid transport and energy metabolism in areas that are infiltrated by tumor cells to a lesser extent. These findings motivate further research directed at investigating the potential of (1)H MRSI to define tumor boundaries in a manner analogous to that of amino acid PET.