Metabolic Imaging of Cerebral Gliomas: Spatial Correlation of Changes in O-(2-18F-Fluoroethyl)-l-Tyrosine PET and Proton Magnetic Resonance Spectroscopic Imaging

The aim of this study was to determine the spatial correlation of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) uptake and the concentrations of choline (Cho), creatine (Cr), and total N-acetylaspartate (tNAA) determined with proton magnetic resonance spectroscopic imaging (1H MRSI) in cerebral gliomas for the multimodal evaluation of metabolic changes. Methods: 18F-FET PET and 2-dimensional 1H MRSI were performed in 15 patients with cerebral gliomas of World Health Organization (WHO) grades II–IV. PET and 1H MRSI datasets were coregistered by use of mutual information. On the basis of their levels of 18F-FET uptake, 4 different areas in a tumor (maximum, strong, moderate, and low 18F-FET uptake) were defined on PET slices as being congruent with the volume of interest in the 1H MRSI experiment. 18F-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 18F-FET uptake, the concentration of tNAA (R = −0.588) and the Cho/tNAA ratio (R = 0.945) correlated significantly with 18F-FET uptake. In the areas with strong and moderate 18F-FET uptake, only the Cho/tNAA ratios (R = 0.811 and R = 0.531, respectively) were significantly associated with amino acid transport. At low 18F-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 1H MRSI and 18F-FET uptake in normal brain tissue. Maximum 18F-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 18F-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 1H MRSI. The significant correlation coefficients detected for Cr in regions with low 18F-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 1H MRSI to define tumor boundaries in a manner analogous to that of amino acid PET.

[1]  M. Kurrer,et al.  18F-FDG and 18F-FET uptake in experimental soft tissue infection , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  B. Weber,et al.  Uptake of 18F-fluorocholine, 18F-fluoro-ethyl-L-tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  C. Manelfe,et al.  Characterization of choline compounds with in vitro 1H magnetic resonance spectroscopy for the discrimination of primary brain tumors. , 1999, Investigative radiology.

[4]  Carles Arús,et al.  Adult primitive neuroectodermal tumor: proton MR spectroscopic findings with possible application for differential diagnosis. , 2002, Radiology.

[5]  M. Schwaiger,et al.  Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  A. Krüger,et al.  O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  Christopher Nimsky,et al.  Preoperative grading of gliomas by using metabolite quantification with high-spatial-resolution proton MR spectroscopic imaging. , 2006, Radiology.

[8]  O. Prante,et al.  Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[10]  Akira Matsumura,et al.  Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction. , 2002, Magnetic resonance imaging.

[11]  K P Pruessmann,et al.  Sensitivity‐encoded spectroscopic imaging , 2001, Magnetic resonance in medicine.

[12]  Karl-Josef Langen,et al.  O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. , 2006, Nuclear medicine and biology.

[13]  K. Zilles,et al.  Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas. , 2003, Nuclear medicine and biology.

[14]  B. Weber,et al.  Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  J. Debus,et al.  Monitoring individual response to brain-tumour chemotherapy: proton MR spectroscopy in a patient with recurrent glioma after stereotactic radiotherapy , 2004, Neuroradiology.

[16]  M. Coel,et al.  Combined Use of F‐18 Fluorocholine Positron Emission Tomography and Magnetic Resonance Spectroscopy for Brain Tumor Evaluation , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[17]  Ewald Moser,et al.  Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1H-MRSI metabolites in gliomas , 2004, NeuroImage.

[18]  K. Hamacher,et al.  O-(2-[18F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[19]  G. Kemp,et al.  Non-Invasive Methods for Studying Brain Energy Metabolism: What They Show and What It Means , 2000, Developmental Neuroscience.

[20]  G. Reifenberger,et al.  Prognostic Value of O-(2-18F-Fluoroethyl)-l-Tyrosine PET and MRI in Low-Grade Glioma , 2007, Journal of Nuclear Medicine.

[21]  N. Shah,et al.  Differential Uptake of O-(2-18F-Fluoroethyl)-l-Tyrosine, l-3H-Methionine, and 3H-Deoxyglucose in Brain Abscesses , 2007, Journal of Nuclear Medicine.

[22]  W. Koch,et al.  Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  M. Kurrer,et al.  Autoradiographic quantification of 18F-FDG uptake in experimental soft-tissue abscesses in rats. , 2002, Radiology.

[24]  H. Amthauer,et al.  123I-IMT SPECT and 1HMR-Spectroscopy at 3.0T in the Differential Diagnosis of Recurrent or Residual Gliomas: A Comparative Study , 2004, Journal of Neuro-Oncology.

[25]  Christopher Nimsky,et al.  Integration of biochemical images of a tumor into frameless stereotaxy achieved using a magnetic resonance imaging/magnetic resonance spectroscopy hybrid data set. , 2004, Journal of neurosurgery.

[26]  H. Herzog,et al.  NEMA NU2-2001 guided performance evaluation of four Siemens ECAT PET scanners , 2003, IEEE Transactions on Nuclear Science.

[27]  T Ido,et al.  Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Ewald Moser,et al.  High‐resolution 3D proton spectroscopic imaging of the human brain at 3 T: SNR issues and application for anatomy‐matched voxel sizes , 2003, Magnetic resonance in medicine.

[29]  G J Barker,et al.  Quantitative analysis of short echo time 1H‐MRSI of cerebral gray and white matter , 2000, Magnetic resonance in medicine.

[30]  Jörg-Christian Tonn,et al.  Value of O-(2-[18F]fluoroethyl)-l-tyrosine PET for the diagnosis of recurrent glioma , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  G. Reifenberger,et al.  Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia. , 2006, Nuclear medicine and biology.

[32]  J. Moffett,et al.  N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology , 2007, Progress in Neurobiology.

[33]  H. Kauczor,et al.  [Metabolic imaging to follow stereotactic radiation of gliomas -- the role of 1H MR spectroscopy in comparison to FDG-PET and IMT-SPECT]. , 2004, RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin.

[34]  G. van Kaick,et al.  Differentiation of radiation necrosis from tumor progression using proton magnetic resonance spectroscopy , 2002, Neuroradiology.

[35]  Karl-Josef Langen,et al.  O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. , 2005, Brain : a journal of neurology.

[36]  J A Frank,et al.  Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET. , 1990, Radiology.

[37]  Hans-Jakob Steiger,et al.  Multimodal metabolic imaging of cerebral gliomas: positron emission tomography with [18F]fluoroethyl-L-tyrosine and magnetic resonance spectroscopy. , 2005, Journal of neurosurgery.

[38]  M Schwaiger,et al.  Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[39]  Rainer Schrader,et al.  Fast and robust registration of PET and MR images of human brain , 2004, NeuroImage.

[40]  R. Goldbrunner,et al.  O-(2-[18F]fluoroethyl)-l-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[41]  O. Prante,et al.  In vitro characterization of the thyroidal uptake of O-(2-[(18)F]fluoroethyl)-L-tyrosine. , 2007, Nuclear medicine and biology.

[42]  G. Reifenberger,et al.  18F-FET PET differentiation of ring-enhancing brain lesions. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[43]  P R Luyten,et al.  Metabolic imaging of patients with intracranial tumors: H-1 MR spectroscopic imaging and PET. , 1990, Radiology.

[44]  W. Koch,et al.  Positron Emission Tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus Magnetic Resonance Imaging in the Diagnosis of Recurrent Gliomas , 2005, Neurosurgery.