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Brain Tumours

The specialist interest area of this group is the preclinical and clinical testing of new radiopharmaceuticals for the diagnosis of brain tumours (i.e., gliomas and metastasis) using Positron-Emission-Tomography (PET) in collaboration with Magnetic Resonance Imaging (MRI) techniques.
This includes the assessment of amino acid uptake in brain tumours in conjunction with modern developments in functional MRI and the clinical application of correlative MR-PET imaging for the diagnosis, therapy planning and therapy control in patients with brain tumours. Additional specialist fields of interest include the evaluation of the therapeutic effects of novel amyloid-β binding peptide ligands using behavioural tests, PET and autoradiography.

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




Highlight 1:

Improved delineation of brain tumours

Magnetic resonance imaging (MRI) is the most important diagnostic tool for assessing brain neoplasms, however, the differentiation of tumour tissue from non-specific post-therapeutic changes after surgery, radio- and chemotherapy in the tissue is difficult. PET, using the radiolabeled amino acid O-(2-[18F]Fluorethyl)-L-tyrosine (FET), provides significant additional information that allows for a more accurate diagnostics of brain tumours. In a study including 132 patients with brain tumours, FET PET allowed the differentiation of recurrent tumour from non-specific post-therapeutic changes with an accuracy of 93%, which clearly demonstrates its superiority over conventional MR imaging.

(Galldiks et al. Neuro Oncol. 2015;17:1293-300)


diffuse astrocytoma


Patient with a diffuse astrocytoma WHO grade II. Follow-up MRI at 86 months after initial diagnosis. MRI shows no contrast enhancement in T1-weighted MRI (left) but an unclear hyperintensity in the T2-weighted MRI (2nd from left) in the right temporal lobe. FET PET (3rd from left) shows a metabolic active tumour recurrence in this area and the time–activity curve was consistent with a highly malignant process. Biopsy of the metabolically active area confirmed a malignant progression to an anaplastic oligoastrocytoma WHO grade III.

Highlight 2:

Correlative Imaging of perfusion-weighted MRT and FET in brain tumours using hybrid PET MRI

PET using FET provides important, additional diagnostic information on the extent of brain tumours to that ascertained using conventional MR imaging. Recent studies suggest that perfusion-weighted MR imaging (PWI), especially maps of regional cerebral blood volume (rCBV), may provide similar diagnostic information. We compared the diagnostic performance of FET PET and PWI-rCBV in a group of 56 patients with different brain tumours using a Hybrid-PET-MR scanner. FET PET showed considerably higher tumour-to-brain contrast and larger tumour volumes than rCBV maps, indicating that metabolically active tumour tissue of brain tumours, as depicted by amino acid PET, is not reflected by rCBV as measured with PWI.


Filß et al. J Nucl Med 2014;55:1–6


diffuse astrocytoma

Hybrid PET/MR imaging study of patient with recurrent WHO grade II oligoastrocytoma after resection and radiation therapy; contrast-enhanced T1-weighted MR imaging on left shows no enhancement in tumour, FET PET (centre) clearly depicts recurrent tumour, and tumour depiction in rCBV map (right) is poor.

References

  • Langen KJ, Galldiks N, Hattingen E, Shah NJ. Advances in neuro-oncology imaging. Nat Rev Neurol. 2017;13:279-289
  • 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. 2017;19:710-718
  • 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-(18)F-Fluoroethyl)-l-Tyrosine Uptake in Rat Gliomas. J Nucl Med. 2017 ;58:700-705
  • 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. 2017 ;44:408-416.
  • 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
  • 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 ;113:158-169
  • Unterrainer M, Galldiks N, Suchorska B, Kowalew LC, Wenter V, Schmid-Tannwald C, Niyazi M, Bartenstein P, Langen KJ, Albert NL. (18)F-FET PET Uptake Characteristics in Patients with Newly Diagnosed and Untreated Brain Metastasis. J Nucl Med. 2017;58:584-589
  • 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 PT, 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. 2017;58:129-137
  • Ceccon G, Stoffels G, Judov N, Filss CP, Rapp M, Bauer E, Hamisch R, 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 PET differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017 1;19:281-288
  • Leithold LHE, Jiang N, Post J, Ziehm T, 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. Pharm Res. 2016 ;33:328-36.
  • Jiang N, Frenzel D, Schartmann E, van Groen T, Kadish I, Shah NJ, Langen KJ, Willbold D, Willuweit A. Blood-brain barrier penetration of an Aβ-targeted, arginine-rich, d-enantiomeric peptide. Biochim Biophys Acta. 2016;1858:2717-2724.
  • Neuschmelting V, Weiss C, Stoffels G, Oros-Peuquens AM; Lockau H, Shah NJ, Langen KJ, Goldbrunner R, Grefkes C. Multimodal Imaging in Malignant Brain Tumors: Enhancing the Preoperative Risk Evaluation for Motor Deficits with a combined Hybrid MR-PET and Navigated TMS Approach. Am J Neuroradiol. 2016;37:266-73
  • Stegmayr C, Willuweit A, Schöneck M, Filß CP, Shah NJ, Coenen HH, Langen KJ. Reproducibility of O-(2-[F-18]Fluoroethyl)-L-tyrosine kinetics in brain tumors and influence of dexamethasone therapy: A PET study in rat gliomas. Eur J Nucl Med Mol Imaging. 2016;43:1115-23.
  • 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/Radionecrosis in high-grade glioma: the diagnostic value of dynamic kinetic O-(2-[18F]fluoroethyl)-L-tyrosine PET imaging FET late progression. Clin Cancer Res. 2016;22:2190-6
  • Leithold LH, Jiang N, Posta 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. European Journal of Pharmaceutical Sciences. Eur J Pharm Sci. 2016;89:31-38
  • Langen KJ and Watts C. Amino Acid PET in Brain Tumor Diagnostics - is it Mature for the Clinic? Nat Rev Neurol. 2016;12:375-6.
  • Dillen KNH, Jacobs HIL, Kukolja J , von Reutern B, Richter N, Onur ÖA, Langen KJ,Fink GRF. Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer’s disease. Neurobiol Aging. 2016;44:114-26.
  • Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, Reifenberger G, Kebir S, Dorn F, Blau T, Herrlinger U, Hau P, Ruge MI, Kocher M, Goldbrunner R, Fink GR, Drzezga A, Schmidt M, Langen KJ. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[(18)F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42:685-95
  • 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
  • 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, 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 ;10:e0128553. doi: 10.1371
  • 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
  • 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 Aβ oligomers. Sci Rep. 2015 Sep 23;5:13222.
  • Rabenstein M, Hucklenbroich J, Willuweit A, Ladwig A, Fink GR, Schroeter M, Langen KJ, Rueger MA. Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4. Stem Cell Res Ther. 2015 May 22;6:99.
  • Geisler S, Beindorff N, Cremer M, Hoffmann K, Brenner W, Cumming P, Meyer PT, Langen KJ, Fuchs E, Buchert R. Characterization of [123I]ioflupane binding to the dopamine transporter in the striatum of tree shrews by quantitative in vitro autoradiography. Synapse. 2015;69:497-504

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. Christian Filß

Cornelia Frey

Dr. Stefanie Geisler

Verena Graf

Natalie Judov

Prof. Dr. K.-J. Langen

Dr. Philipp Lohmann

Trude Plum

Michael Schöneck

Dr. Carina Stegmayr

Dr. Gabriele Stoffels

Dr. Antje Willuweit





Group Photo

Address

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


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