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.
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- Leithold LH, Jiang N, Post J, Ziehm T, Schartmann E, Kutzsche J, Shah NJ, Breitkreutz J, Langen KJ, Willuweit A, Willbold D. Pharmacokinetic Properties of a Novel D-Peptide Developed to be Therapeutically Active Against Toxic β-Amyloid Oligomers. Pharm Res. 2015 Sep 17. [Epub ahead of print] PubMed PMID: 26381279.
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- Lohmann P, Herzog H, Rota Kops E, Stoffels G, Filss C, Galldiks N, Coenen HH, Shah NJ , Langen KJ. Changes of biological tumor volume of glioma patients in early and late O-(2-[18F]fluoroethyl)-L-tyrosine PET scans. Eur J Radiol 2015;25:3017-24.
- Galldiks N and Langen KJ. Applications of PET imaging of neurological tumors with radiolabeled amino acids. Invited review. Q J Nucl Med Mol Imaging 2015;59:70-82.
- Dunkl V, Cleff C, Stoffels G, Sarikaya-Seiwert S, Fink GR, Coenen HH, Langen KJ, Galldiks N. The use of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine-PET in the clinical evaluation of brain tumors in children and young adults. J Nucl Med. 2015;56:88-92.
- Weiss C, Tursunova I, Neuschmelting V, Lockau H, Nettekoven C, Oros-Peusquens AM, Stoffels G, Rehme AK, Faymonville AM, Shah NJ, Langen KJ, Goldbrunner R, Grefkes C. Improved nTMS- and DTI-derived CST tractography through anatomical ROI seeding on anterior pontine level compared to internal capsule. Neuroimage Clin. 2015; 7:424-37
- Cicone F, Filss CP, Minniti G, Rossi-Espagnet C, Papa A, Scaringi C, Bozzao A, Scopinaro F and Langen KJ. Volumetric assessment of progressive gliomas: comparison between F-DOPA PET and perfusion-MRI. Eur J Nucl Med Mol Imaging. 2015; 42:905-915
- Galldiks N, Stoffels G, Filss C, Dunkl V, Rapp M, Blau T, Tscherpel C, Ceccon G, Dunkl V, Winzierl M, Stoffel M, Sabel M, Fink GR, Shah N.J. Langen KJ. The use of dynamic O-(2-18F-fluoroethyl)-L-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro Oncol. 2015;17:1293-300.
- Jiang N, Leithold LHE, Post J, Ziehm T, Mauler J, Langen KJ, Breitkreuz J, Willbold D, Willuweit A. Preclinical pharmacokinetic studies of the tritium labelled D-enantiomeric peptide D3 developed for the treatment of Alzheimer´s disease. PLoS One. 2015 Jun 5;10(6):e0128553. doi: 10.1371
- Geisler S, Ermert J, Stoffels G, Willuweit A, Galldiks N, Shah NJ, Coenen HH, Langen KJ. Isomers of 4-[18F]Fluoro-Proline: Radiosynthesis, biological evaluation and first results in humans using PET. Curr Radiopharm. 2014 2014;7:123-32
- Filss CP, Wittsack HJ, Galldiks N, Stoffels G, Sabel M, Coenen HH, Shah NJ, Herzog H, Langen KJ. Comparison of 18F-FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. J Nucl Med. 2014; 55:540-5