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Brain Tumors

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.

http://www.wirkstoffforschung.helmholtz.de/de/partner/forschungszentrum_juelich_fzj/




Highlight 1:

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)

Verbesserte Abgrenzung von Hirntumoren

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.

Highlight 2:

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


Frühzeitige Beurteiling des Therapieerolgs bei Hirntumoren

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.

References

  • Langen KJ, Galldiks N, Hattingen E, Shah NJ. Advances in neuro-oncology imaging. Nat Rev Neurol. 2017 Apr 7. doi: 10.1038/nrneurol.2017.44. [Epub ahead of print] Review. PubMed PMID: 28387340.
  • Heinzel A, Müller D, Yekta-Michael SS, Ceccon G, Langen KJ, Mottaghy FM, Wiesmann M, Kocher M, Hattingen E, Galldiks N. O-(2-18F-fluoroethyl)-L-tyrosine
    PET for evaluation of brain metastasis recurrence after radiotherapy: an effectiveness and cost-effectiveness analysis. Neuro Oncol. 2017 Feb 13. doi: 10.1093/neuonc/now310. [Epub ahead of print] PubMed PMID: 28204572.
  • Stegmayr C, Oliveira D, Niemietz N, Willuweit A, Lohmann P, Galldiks N, Shah NJ, Ermert J, Langen KJ. Influence of bevacizumab on blood-brain barrier permeability and O-(2-18F-fluoroethyl)-L-tyrosine uptake in rat gliomas. J Nucl Med. 2017 Feb 2. pii: jnumed.116.187047. doi: 10.2967/jnumed.116.187047. [Epub ahead of print] PubMed PMID: 28153956.
  • Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, Bauer E, Hamisch
    C, Ruge MI, Kocher M, Kuchelmeister K, Sellhaus B, Sabel M, Fink GR, Shah NJ,
    Langen KJ, Galldiks N. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017 Feb 1;19(2):281-288. doi: 10.1093/neuonc/now149. PubMed PMID: 27471107.
  • Weiss Lucas C, Tursunova I, Neuschmelting V, Nettekoven C, Oros-Peusquens AM, Stoffels G, Faymonville AM, Shah NJ, Langen KJ, Lockau H, Goldbrunner R, Grefkes C. Functional MRI vs. navigated TMS to optimize M1 seed volume delineation for DTI tractography. A prospective study in patients with brain tumours adjacent to the corticospinal tract. Neuroimage Clin. 2016 Nov 23;13:297-309. doi: 10.1016/j.nicl.2016.11.022. PubMed PMID: 28050345.
  • Cicone F, Galldiks N, Minniti G, Filss CP, Scopinaro F, Prior JO, Albert NL, Langen KJ. Comment on Hatzoglou et al: Dynamic contrast-enhanced MRI perfusion versus 18FDG PET/CT in differentiating brain tumor progression from radiation injury. Neuro Oncol. 2016 Dec 31. pii: now283. doi: 10.1093/neuonc/now283. [Epub ahead of print] PubMed PMID: 28040712.
  • Tscherpel C, Dunkl V, Ceccon G, Stoffels G, Judov N, Rapp M, Meyer PT, Kops ER, Ermert J, Fink GR, Shah NJ, Langen KJ, Galldiks N. The use of O-(2-18F-fluoroethyl)-L-tyrosine PET in the diagnosis of gliomas located in the brainstem and spinal cord. Neuro Oncol. 2016 Dec 29. pii: now243. doi: 10.1093/neuonc/now243. [Epub ahead of print] PubMed PMID: 28039366.
  • Linden M, Helmbold K, Kempf J, Sippas S, Filss C, Langen KJ, Eisert A, Zepf FD. Dietary tryptophan depletion in humans using a simplified two amino acid formula - a pilot study. Food Nutr Res. 2016 Dec 16;60:29272. doi: 10.3402/fnr.v60.29272. PubMed PMID: 27989269; PubMed Central PMCID: PMC5165058.
  • Lohmann P, Stoffels G, Ceccon G, Rapp M, Sabel M, Filss CP, Kamp MA, Stegmayr C, Neumaier B, Shah NJ, Langen KJ, Galldiks N. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase (18)F-FET PET accuracy without dynamic scans. Eur Radiol. 2016 Nov 16. [Epub ahead of print] PubMed PMID: 27853813.
  • Lohmann P, Willuweit A, Neffe AT, Geisler S, Gebauer TP, Beer S, Coenen HH, Fischer H, Hermanns-Sachweh B, Lendlein A, Shah NJ, Kiessling F, Langen KJ. Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect. Biomaterials. 2017 Jan;113:158-169. doi: 10.1016/j.biomaterials .2016.10.039. PubMed PMID: 27815999.
  • Unterrainer M, Galldiks N, Suchorska B, Kowalew LC, Wenter V, Schmid-Tannwald C, Niyazi M, Bartenstein P, Langen KJ, Albert NL. 18F-FET PET uptake characteristics in patients with newly diagnosed and untreated brain metastasis. J Nucl Med. 2016 Oct 6. pii: jnumed.116.180075. PubMed PMID: 27754904.
  • Stegmayr C, Bandelow U, Oliveira D, Lohmann P, Willuweit A, Filss C, Galldiks N, Lübke JH, Shah NJ, Ermert J, Langen KJ. Influence of blood-brain barrier permeability on O-(2-(18)F-fluoroethyl)-L-tyrosine uptake in rat gliomas. Eur J Nucl Med Mol Imaging. 2016 Sep 9. [Epub ahead of print] PubMed PMID: 27613541.
  • Kebir S, Rauschenbach L, Galldiks N, Schlaak M, Hattingen E, Landsberg J, Bundschuh RA, Langen KJ, Scheffler B, Herrlinger U, Glas M. Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine PET imaging for the detection of checkpoint
    inhibitor-related pseudoprogression in melanoma brain metastases. Neuro Oncol. 2016 Oct;18(10):1462-4. doi: 10.1093/neuonc/now154. Epub 2016 Sep 2. PubMed PMID: 27591333; PubMed Central PMCID: PMC5035529.
  • Watts C, Langen KJ. PET imaging in glioma: is it time for mainstream practice? Neuro Oncol. 2016 Sep;18(9):1193-4. doi: 10.1093/neuonc/now134. PubMed PMID: 27563104; PubMed Central PMCID: PMC4999004.
  • Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, Bauer E, HamischC, Ruge MI, Kocher M, Kuchelmeister K, Sellhaus B, Sabel M, Fink GR, Shah NJ, Langen KJ, Galldiks N. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission
    tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2016 Jul 28. pii: now149. [Epub ahead of print] PubMed PMID: 27471107.
  • Hutterer M, Ebner Y, Riemenschneider MJ, Willuweit A, McCoy M, Egger B, Schröder M, Wendl C, Hellwig D, Grosse J, Menhart K, Proescholdt M, Fritsch B, Urbach H, Stockhammer G, Roelcke U, Galldiks N, Meyer P, Langen KJ, Hau P, Trinka E. Epileptic activity increases cerebral amino acid transport assessed by [18F]-fluoroethyl-L-tyrosine amino acid PET - a potential brain tumor mimic. J Nucl Med. 2016 Jul 28. pii: jnumed.116.176610. [Epub ahead of print] PubMed PMID:27469356.
  • Leithold LH, Jiang N, Post J, Niemietz N, Schartmann E, Ziehm T, Kutzsche J, Shah NJ, Breitkreutz J, Langen KJ, Willuweit A, Willbold D. Pharmacokinetic properties of tandem d-peptides designed for treatment of Alzheimer's disease. Eur J Pharm Sci. 2016 Apr 13. pii: S0928-0987(16)30119-1. doi: 10.1016/j.ejps.2016.04.016. [Epub ahead of print] PubMed PMID: 27086111.
  • Barthel H, Meyer PT, Drzezga A, Bartenstein P, Boecker H, Brust P, Buchert R, Coenen HH, la Fougère C, Gründer G, Grünwald F, Krause BJ, Kuwert T, Schreckenberger M, Tatsch K, Langen KJ, Sabri O. [German Society of Nuclear Medicine procedure guideline on beta-amyloid brain PET imaging]. Nuklearmedizin. 2016 Apr 15;55(4). [Epub ahead of print] German. PubMed PMID: 27080914.
  • Mendes AC, Ribeiro AS, Oros-Peusquens AM, Langen KJ, Shah J, Ferreira HA. Brain connectivity study of brain tumor patients using MR-PET data: preliminary results. EJNMMI Phys. 2015 Dec;2(Suppl 1):A75. doi: 10.1186/2197-7364-2-S1-A75. PubMed PMID: 26956336; PubMed Central PMCID: PMC4798682.
  • Neuner I, Mauler J, Arrubla J, Kops ER, Tellmann L, Scheins J, Herzog H, Langen KJ, Shah J. Simultaneous trimodal MR-PET-EEG imaging for the investigation of resting state networks in humans. EJNMMI Phys. 2015 Dec;2(Suppl 1):A71. doi: 10.1186/2197-7364-2-S1-A71. PubMed PMID: 26956332.
  • Mauler J, Langen KJ, Maudsley AA, Nikoubashman O, Filss C, Stoffels G, Shah NJ. Congruency of tumour volume delineated by FET PET and MRSI. EJNMMI Phys. 2015 Dec;2(Suppl 1):A61. doi: 10.1186/2197-7364-2-S1-A61. PubMed PMID: 26956321; PubMed Central PMCID: PMC4798678.
  • da Silva NA, Caldeira L, Herzog H, Tellmann L, Filss C, Langen KJ, Shah J. Automatic derivation of an MR-PET image-based input function for quantification of 18F-FET. EJNMMI Phys. 2015 Dec;2(Suppl 1):A27. doi:
    10.1186/2197-7364-2-S1-A27. PubMed PMID: 26956283; PubMed Central PMCID: PMC4798701.
  • Kebir S, Fimmers R, Galldiks N, Schäfer N, Mack F, Schaub C, Stuplich M, Niessen M, Tzaridis T, Simon M, Stoffels G, Langen KJ, Scheffler B, Glas M, Herrlinger U. Late Pseudoprogression in Glioblastoma: Diagnostic Value of Dynamic O-(2-[18F]fluoroethyl)-L-Tyrosine PET. Clin Cancer Res. 2015 Dec 16. [Epub ahead of print] PubMed PMID: 26673798.
  • Stegmayr C, Schöneck M, Oliveira D, Willuweit A, Filss C, Galldiks N, Shah NJ, Coenen HH, Langen KJ. Reproducibility of O-(2-(18)F-fluoroethyl)-L-tyrosine uptake kinetics in brain tumors and influence of corticoid therapy: an experimental study in rat gliomas. Eur J Nucl Med Mol Imaging. 2015 Dec 8. [Epub ahead of print] PubMed PMID: 26646781.
  • Brener O, Dunkelmann T, Gremer L, van Groen T, Mirecka EA, Kadish I, Willuweit A, Kutzsche J, Jürgens D, Rudolph S, Tusche M, Bongen P, Pietruszka J, Oesterhelt F, Langen KJ, Demuth HU, Janssen A, Hoyer W, Funke SA, Nagel-Steger L, Willbold D. QIAD assay for quantitating a compound's efficacy in elimination of toxic A? oligomers. Sci Rep. 2015 Sep 23;5:13222. doi: 10.1038/srep13222. PubMed PMID: 26394756; PubMed Central PMCID: PMC4585794.
  • 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 ?-Amyloid Oligomers. Pharm Res. 2015 Sep 17. [Epub ahead of print] PubMed PMID: 26381279.
  • Galldiks N, Langen KJ, Pope WB. From the clinician's point of view - What is the status quo of positron emission tomography in patients with brain tumors? Neuro Oncol. 2015 Jun 30. pii: nov118. [Epub ahead of print] Review. PubMed PMID: 26130743.
  • 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

Additional Information

Brain Tumors

Teamleader

Prof. Dr. med. K.J. Langen

Building: 15.2, Raum: 372

Tel.:  +49-2461-61-5900
Fax: +49-2461-61-8261
k.j.langen@fz-juelich.de

Members

Dr. med. Christian Filß

Stefanie Geisler

Natalie Judov

Sibille Kremer

Prof. Dr. med. K.-J. Langen

Philipp Lohmann

Nicole Niemietz

Michael Schöneck

Carina Stegmayr

Dr. med. Gabriele Stoffels

Dr. rer. nat. Antje Willuweit





Group Photo

Address

Institut für Neurowissenschaften und Medizin (INM-4)
Forschungszentrum Jülich
52425 Jülich
Gebäude: 15.2


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