The special field of interest of this group is the preclinical and clinical testing of new radiopharmaceuticals for nuclear medicine diagnostics of brain tumors using Positron-Emission-Tomography (PET) and correlation with Magnetic Resonance Imaging (MRI). This includes the assessment of amino acid uptake in brain tumors in correlation with modern developments of functional MRI and the clinical application of correlative MR-PET imaging for the diagnosis, therapy planning and therapy control in patients with brain tumors. Another topic is the evaluation of therapeutic effects of novel amyloid- β binding peptide ligands using behavioral tests, PET and autoradiography.
Improved delineation of brain tumors
Magnetic resonance (MR) imaging is the most important diagnostic tool for assessing brain neoplasms but the differentiation of tumour tissue from unspecific changes in the surrounding tissue is difficult. PET using radiolabeled amino acids yields significant additional information that allows for a more accurate diagnostics of cerebral gliomas. With the newly developed amino acid O-(2-[18F]Fluorethyl)-L-tyrosin (FET) a widespread clinical application of this method is possible. In a biopsy-controlled study using FET PET and MRI in patients with suspected cerebral glioma MRI yielded a sensitivity of 96 % for the detection of tumour but a specificity of only 53 %. In contrast, the combined use of MRI and FET PET increased specificity to 94 % with a sensitivity of 93 %. This demonstrated a significant improvement of diagnostic accuracy (Pauleit et al. Brain 2005 ;128:678-87)
Anaplastic Astrocytoma WHO Grade III. T1-weighted MRI after application of Gd-DTPA (left) and T2 weighted MRI shows widespread abnormalities but does not allow a delineation of the tumour. FET PET (right) clearly depicts the tumour while glucose metabolism (FDG PET) is decreased in the tumor area.
Early assessment of treatment response in brain tumors
The diagnostic value of MRI and CT concerning in the early stage after radiochemotherapy is limited because non-specific contrast enhancement may mimic tumor progression (pseudoprogression) and can lead to an unnecessary overtreatment. In a recent study we evaluated the
prognostic value of early changes of 18FFET uptake after postoperative radiochemotherapy in glioblastomas. It could be demonstrated that PET responders with a decrease of the tumor/brain ratio of more than 10% had a significantly longer disease-free survival and overall survival (OS) than patients with stable or increasing tracer uptake after radiochemotherapy in glioblastomas.
Galldiks et al. J Nucl Med 2012;53:1048-57
Glioblastoma WHO grade IV. After surgery (upper row) FET PET shows residual tumour tissue (red area) which exhibits no contrast enhancement in MRI (left). Two months after completion of radiochemotherapy (middle row) MRI shows contrast enhancement indicating tumour progression. Further control after 3 months (lower row) confirms good therapy response and shrinkage of the tumour.
- Galldiks N, Rapp, Fink GR, Shah NJ, Coenen HH, Sabel M, Langen KJ. Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging. 2013;40:22-33.
- Rapp M, Heinzel A, Galldiks N, Stoffels G, Felsberg J, Ewelt C, Sabel M, Steiger HJ, Reifenberger G, Beez T, Coenen HH, Floeth FW, Langen KJ. Diagnostic Performance of 18F-FET PET in Newly Diagnosed Cerebral Lesions Suspicious for Glioma, J Nucl Med 2013;54:229-235
- Geisler S, Willuweit A, Schroeter M, Zilles K, Hamacher K, Coenen HH, Shah NJ, Langen KJ. Cis-4-[F18]fluoro-D-proline detects secondary thalamic and hippocampal degeneration induced by rat glioma. JCBFM 2013;33:724-31.
- Galldiks N, Rapp M, Stoffels G, Dunkl V, Sabel M, Langen KJ. Earlier Dagnosis of Progressive Disease during Bevacizumab Treatment Using O-(2-18F-Fluorethyl)-L-tyrosine PET in Comparison to MRI. Molecular Imaging 2013;12:273-6
- Piroth MD, Prasath J, Willuweit A, Stoffels G, Sellhaus B, van Osterhout A, Klein S, Shah NJ, Eble M, Coenen HH, Langen KJ. Uptake of O-(2-[18F]fluoroethyl)-L-tyrosine in reactive astrocytosis in the vicinity of untreated and irradiated cerebral gliomas. Nucl Med Biol. 2013;40:795-800.
- Heinzel A, Müller D, Langen KJ, Blaum M, Verburg FA, Galldiks N. The use of O-(2-18F-Fluoroethyl)-L-tyrosine PET for treatment management of bevacizumab and irinotecan in patients with recurrent high-grade glioma: A cost-effectiveness analysis, J Nucl Med. 2013 ;54:1217-22
- Floeth FW, Galldiks N, Eicker S, Stoffels G, Herdmann J, Steiger HJ, Antoch MD, Rhee S, Langen KJ. Focal Hypermetabolism in 18F-FDG PET Indicates Temporary Recovery Potential in Patients with Cervical Myelopathy. J Nucl Med. 2013 54:1577-1583
Galldiks N, Stoffels G, Ruge MI, Sabel M, Reifenberger G, Zuhal E, Shah NJ, Fink GR, Coenen HH, Langen KJ. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET as diagnostic tool for malignant transformation in patients with low-grade glioma. J Nucl Med. 2013;54:2046-54