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Teilprojekt C06

Multiparametrische Bildgebung vaskulärer Pathologien

Teilprojektleiter: Sven Hermann (seit 07/2013), Bodo Levkau, Michael Schäfers
Ehemaliger Teilprojektleiter: Otmar Schober (07/2009-06/2013)
Projektlaufzeit: 07/2009 – 06/2017

Projekt

Arteriosklerose liegt einer Vielzahl vaskulärer Pathologien und der Mehrzahl kardiovaskulärer Ereignisse zugrunde, sie ist durch spezifische entzündlich-degenerative Prozesse in der arteriellen Gefäßwand charakterisiert. Auf Grundlage der Ergebnisse der letzten Förderperiode zielt das Arbeitsprogramm dieses Projekts auf die multiparametrische Bildgebung in Mausmodellen fortgeschrittener/vulnerabler Plaques in den Carotiden und den Koronarien ab. Als langfristiges Ziel verfolgt das Teilprojekt die Translation der präklinischen Plaque-Bildgebung zu klinischer Diagnostik, z.B. bei Patienten vor Carotis-Endatherektomien.

Im Teilprojekt C06 entstandene Publikationen

2018

Axer A, Hermann S, Kehr G, Clases D, Karst U, Fischer-Riepe L, Roth J, Fobker M, Schafers M, Gilmour R, Faust A. Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design. ChemMedChem 2018;13: 241-250. Abstract
Butsch V, Borgel F, Galla F, Schwegmann K, Hermann S, Schafers M, Riemann B, Wunsch B, Wagner S. Design, (Radio)Synthesis, and in Vitro and in Vivo Evaluation of Highly Selective and Potent Matrix Metalloproteinase 12 (MMP-12) Inhibitors as Radiotracers for Positron Emission Tomography. J Med Chem 2018;61: 4115-4134. Abstract
Gran S, Honold L, Fehler O, Zenker S, Eligehausen S, Kuhlmann MT, Geven E, den Bosch M van, van Lent P, Spiekermann C, Hermann S, Vogl T, Schäfers M, Roth J. Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment_in vivo_. Theranostics 2018;8: 2407-2423. Abstract
Hohn M, Chang M, Meisel JE, Frost E, Schwegmann K, Hermann S, Schäfers M, Riemann B, Haufe G, Breyholz HJ, Wagner S. Synthesis and preliminary in vitro and in vivo evaluation of thiirane-based slow binding MMP inhibitors as potential radiotracers for PET imaging. Chemistry Select 2018;3: 11729-11736. Abstract
Hugenberg V, Behrends M, Wagner S, Hermann S, Schafers M, Kolb HC, Szardenings K, Walsh JC, Gomez LF, Kopka K, Haufe G. Synthesis, radiosynthesis, in vitro and first in vivo evaluation of a new matrix metalloproteinase inhibitor based on gamma-fluorinated alpha-sulfonylaminohydroxamic acid. EJNMMI Radiopharm Chem 2018;3: 10. Abstract

2017

Hugenberg V, Wagner S, Kopka K, Schafers M, Schuit RC, Windhorst AD, Hermann S. Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation. J Med Chem 2017;60: 307-321. Abstract
Seifert R, Scherzinger A, Kiefer F, Hermann S, Jiang X, Schafers MA. Statistical Permutation-based Artery Mapping (SPAM): a novel approach to evaluate imaging signals in the vessel wall. BMC Med Imaging 2017;17: 36. Abstract
Van de Vyver H, Bovenkamp PR, Hoerr V, Schwegmann K, Tuchscherr L, Niemann S, Kursawe L, Grosse C, Moter A, Hansen U, Neugebauer U, Kuhlmann MT, Peters G, Hermann S, Loffler B. A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection: Noninvasive Imaging of Biofilm Development in Vivo. Am J Pathol 2017;187: 268-279. Abstract

2016

Buther F, Vehren T, Schafers KP, Schafers M. Impact of Data-driven Respiratory Gating in Clinical PET. Radiology 2016: 152067. Abstract
Hermann S, Kuhlmann MT, Starsichova A, Eligehausen S, Schafers K, Stypmann J, Tiemann K, Levkau B, Schafers M. Imaging Reveals the Connection Between Spontaneous Coronary Plaque Ruptures, Atherothrombosis, and Myocardial Infarctions in HypoE/SRBI-/- Mice. J Nucl Med 2016;57: 1420-1427. Abstract
Hugenberg V, Hermann S, Galla F, Schafers M, Wunsch B, Kolb HC, Szardenings K, Lebedev A, Walsh JC, Mocharla VP, Gangadharmath UB, Kopka K, Wagner S. Radiolabeled hydroxamate-based matrix metalloproteinase inhibitors: How chemical modifications affect pharmacokinetics and metabolic stability. Nucl Med Biol 2016;43: 424-437. Abstract
Vrachimis A, Honold L, Faust A, Hermann S, Schafers M. New molecular probes of vascular inflammation. Q J Nucl Med Mol Imaging 2016;60: 194-204. Abstract

2015

Limpachayaporn P, Schafers M, Haufe G. Isatin sulfonamides: potent caspases-3 and -7 inhibitors, and promising PET and SPECT radiotracers for apoptosis imaging. Future Med Chem 2015;7: 1173-1196. Abstract
Santschi N, Wagner S, Daniliuc C, Hermann S, Schafers M, Gilmour R. Synthesis of 2-[(18) F]Fluoro-2-deoxyisosorbide 5-mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET). ChemMedChem 2015;10: 1724-1732. Abstract
Shaikh RS, Keul P, Schäfers M, Levkau B, Haufe G. New fluorinated agonists for targeting the sphingosin-1-phosphate receptor 1 (S1P1). Bioorganic & Medicinal Chemistry Letters 2015;25: 5048-5051. Abstract
Shaikh RS, Schilson SS, Wagner S, Hermann S, Keul P, Levkau B, Schafers M, Haufe G. Synthesis and evaluation of fluorinated fingolimod (FTY720) analogues for sphingosine-1-phosphate receptor molecular imaging by positron emission tomography. J Med Chem 2015;58: 3471-3484. Abstract
Wenning C, Vrachimis A, Dell Aquila A, Penning A, Stypmann J, Schafers M. Inhomogeneous myocardial stress perfusion in SPECT studies predicts future allograft dysfunction in heart transplant recipients. EJNMMI Res 2015;5: 51. Abstract

2014

Persigehl T, Ring J, Bremer C, Heindel W, Holtmeier R, Stypmann J, Claesener M, Hermann S, Schafers M, Zerbst C, Schliemann C, Mesters RM, Berdel WE, Schwoppe C. Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF-NGR using multi-modal imaging. Angiogenesis 2014;17: 235-246. Abstract
van Duijnhoven SMJ, Robillard MS, Hermann S, Kuhlmann MT, Schafers M, Nicolay K, Grull H. Imaging of MMP activity in postischemic cardiac remodeling using radiolabeled MMP-2/9 activatable peptide probes. Mol Pharm 2014;11: 1415-1423. Abstract
Wenning C, Kloth C, Kuhlmann MT, Jacobs AH, Schober O, Hermann S, Schafers MA. Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis. Atherosclerosis 2014;234: 276-282. Abstract

2013

Diepenbrock S, Hermann S, Schäfers M, Kuhlmann M, Hinrichs K. Comparative Visualization of Tracer Uptake in In Vivo Small Animal PET/CT Imaging of the Carotid Arteries. Comput Graph Forum 2013;32: 241-250. Abstract
Grabner A, Kentrup D, Edemir B, Sirin Y, Pavenstadt H, Schlatter E, Schober O, Schafers M, Schnockel U, Reuter S. PET with 18F-FDG-labeled T lymphocytes for diagnosis of acute rat renal allograft rejection. J Nucl Med 2013;54: 1147-1153. Abstract
Grabner A, Kentrup D, Schnockel U, Gabriels G, Schroter R, Pavenstadt H, Schober O, Schlatter E, Schafers M, Reuter S. Non-invasive imaging of acute allograft rejection after rat renal transplantation using 18F-FDG PET. J Vis Exp 2013: e4240. Abstract
Hahnenkamp A, Schäfers M, Bremer C, Höltke C. Design and Synthesis of Small-Molecule Fluorescent Photoprobes Targeted to Aminopeptdase N (APN/CD13) for Optical Imaging of Angiogenesis. Bioconjug Chem 2013;24: 1027-1038. Abstract
Hermann S, Pichler B, Kotzerke J. [Preclinical research Seal of approval translational medicine]. Nuklearmedizin 2013;52: N53-4. Abstract
Hugenberg V, Riemann B, Hermann S, Schober O, Schafers M, Szardenings K, Lebedev A, Gangadharmath U, Kolb H, Walsh J, Zhang W, Kopka K, Wagner S. Inverse 1,2,3-triazole-1-yl-ethyl substituted hydroxamates as highly potent matrix metalloproteinase inhibitors: (radio)synthesis, in vitro and first in vivo evaluation. J Med Chem 2013;56: 6858-6870. Abstract
Limpachayaporn P, Wagner S, Kopka K, Hermann S, Schäfers M, Haufe G. Synthesis, 18F-radiolabeling, and in vivo biodistribution studies of N-fluorohydroxybutyl isatin sulfonamides using positron emission tomography. J Med Chem 2013;56: 4509-4520. Abstract
Stegger L, Schülke C, Wenning C, Rahbar K, Kies P, Schober O, Schäfers M. Cardiac PET/MRI. Curr Cardiovasc Imaging Rep 2013: 1-10. Abstract
Waschkau B, Faust A, Schäfers M, Bremer C. Performance of a new fluorescence-labeled MMP inhibitor to image tumor MMP activity in vivo in comparison to an MMP-activatable probe. Contrast Media Mol Imaging 2013;8: 1-11. Abstract
Würslin C, Schmidt H, Martirosian P, Brendle C, Boss A, Schwenzer NF, Stegger L. Respiratory Motion Correction in Oncologic PET Using T1-Weighted MR Imaging on a Simultaneous Whole-Body PET/MR System. J Nucl Med 2013;54: 464-471. Abstract

2012

Claesener M, Breyholz H-J, Hermann S, Faust A, Wagner S, Schober O, Schäfers M, Kopka K. Efficient synthesis of a fluorine-18 labeled biotin derivative. Nucl Med Biol 2012;39: 1189-1194. Abstract
Hermann S, Starsichova A, Waschkau B, Kuhlmann M, Wenning C, Schober O, Schäfers M. Non-FDG imaging of atherosclerosis: Will imaging of MMPs assess plaque vulnerability?. J Nucl Cardiol 2012;19: 609-617. Abstract
Hugenberg V, Breyholz H-J, Riemann B, Hermann S, Schober O, Schäfers M, Gangadharmath U, Mocharla V, Kolb H, Walsh J, Zhang W, Kopka K, Wagner S. A new class of highly potent matrix metalloproteinase inhibitors based on triazole-substituted hydroxamates: (radio)synthesis and in vitro and first in vivo evaluation. J Med Chem 2012;55: 4714-4727. Abstract
Kuhlmann MT, Cuhlmann S, Hoppe I, Krams R, Evans PC, Strijkers GJ, Nicolay K, Hermann S, Schäfers M. Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice. J Vis Exp 2012: 3308. Abstract
Paul M, Rahbar K, Gerss J, Kies P, Schober O, Schäfers K, Breithardt G, Schulze-Bahr E, Wichter T, Schäfers M. Microvascular dysfunction in nonfailing arrhythmogenic right ventricular cardiomyopathy. Eur J Nucl Med Mol Imaging 2012;39: 416-420. Abstract
Paulis LE, Geelen T, Kuhlmann MT, Coolen BF, Schäfers M, Nicolay K, Strijkers GJ. Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery. J Control Release 2012;162: 276-285. Abstract
Rahbar K, Seifarth H, Schäfers M, Stegger L, Hoffmeier A, Spieker T, Tiemann K, Maintz D, Scheld HH, Schober O, Weckesser M. Differentiation of malignant and benign cardiac tumors using 18F-FDG PET/CT. J Nucl Med 2012;53: 856-863. Abstract
Schwenzer NF, Stegger L, Bisdas S, Schraml C, Kolb A, Boss A, Müller M, Reimold M, Ernemann U, Claussen CD, Pfannenberg C, Schmidt H. Simultaneous PET/MR imaging in a human brain PET/MR system in 50 patients - Current state of image quality. Eur J Radiol 2012;81: 3472-3478. Abstract
Stegger L, Martirosian P, Schwenzer N, Bisdas S, Kolb A, Pfannenberg C, Claussen CD, Pichler B, Schick F, Boss A. Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI. Acta Radiol 2012;53: 1066-1072. Abstract
Vrachimis A, Hermann S, Mathe D, Schober O, Schäfers M. Systematic evaluation of 99mTc-tetrofosmin versus 99mTc-sestamibi to study murine myocardial perfusion in small animal SPECT/CT. EJNMMI Res 2012;2: 21. Abstract
Wenning C, Stypmann J, Papavassilis P, Sindermann J, Schober O, Hoffmeier A, Scheld HH, Stegger L, Schäfers M. Left ventricular dilation and functional impairment assessed by gated SPECT are indicators of cardiac allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant 2012;31: 719-728. Abstract

2011

Baumann A, Faust A, Law MP, Kuhlmann MT, Kopka K, Schäfers M, Karst U. Metabolite identification of a radiotracer by electrochemistry coupled to liquid chromatography with mass spectrometric and radioactivity detection. Anal Chem 2011;83: 5415-5421. Abstract
Boss A, Stegger L, Bisdas S, Kolb A, Schwenzer N, Pfister M, Claussen CD, Pichler BJ, Pfannenberg C. Feasibility of simultaneous PET/MR imaging in the head and upper neck area. Eur Radiol 2011;21: 1439-1446. Abstract
Michel K, Büther K, Law MP, Wagner S, Schober O, Hermann S, Schäfers M, Riemann B, Höltke C, Kopka K. Development and evaluation of endothelin-A receptor (radio)ligands for positron emission tomography. J Med Chem 2011;54: 939-948. Abstract
Wagner S, Faust A, Breyholz H-J, Schober O, Schäfers M, Kopka K. The MMP inhibitor (R)-2-(N-benzyl-4-(2-[18F]fluoroethoxy)phenylsulphonamido)-N-hydroxy-3-met hylbutanamide: Improved precursor synthesis and fully automated radiosynthesis. Appl Radiat Isot 2011;69: 862-868. Abstract
Wenning C, Stegger D, Hermann S, Schober O, Schäfers M. F-18-FDG Imaging for Atherosclerotic Plaque Characterization. Curr Cardiovasc Imaging Rep 2011;4: 190-198. Abstract

2010

Boss A, Bisdas S, Kolb A, Hofmann M, Ernemann U, Claussen CD, Pfannenberg C, Pichler BJ, Reimold M, Stegger L. Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT. J Nucl Med 2010;51: 1198-1205. Abstract
Bovens S, Schulze Elfringhoff A, Kaptur M, Reinhardt D, Schäfers M, Lehr M. 1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A(2)alpha: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability. J Med Chem 2010;53: 8298–8308. Abstract
Breyholz HJ, Wagner S, Faust A, Riemann B, Höltke C, Hermann S, Schober O, Schäfers M, Kopka K. Radiofluorinated pyrimidine-2,4,6-triones as molecular probes for noninvasive MMP-targeted imaging. ChemMedChem 2010;5: 777-789. Abstract
Buscher K, Judenhofer MS, Kuhlmann MT, Hermann S, Wehrl HF, Schäfers KP, Schäfers M, Pichler BJ, Stegger L. Isochronous assessment of cardiac metabolism and function in mice using hybrid PET/MRI. J Nucl Med 2010;51: 1277-1284. Abstract
Büther F, Ernst I, Dawood M, Kraxner P, Schäfers M, Schober O, Schäfers KP. Detection of respiratory tumour motion using intrinsic list mode-driven gating in positron emission tomography. Eur J Nucl Med Mol Imaging 2010;37: 2315-2327. Abstract
Drews A, Bovens S, Roebrock K, Sunderkotter C, Reinhardt D, Schäfers M, van der Velde A, Schulze Elfringhoff A, Fabian J, Lehr M. 1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A(2)alpha with reduced lipophilicity: synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activity. J Med Chem 2010;53: 5165-5178. Abstract
Law MP, Wagner S, Kopka K, Renner C, Pike VW, Schober O, Schäfers M. Preclinical evaluation of an 18F-labelled beta1-adrenoceptor selective radioligand based on ICI 89,406. Nucl Med Biol 2010;37: 517-526. Abstract
Range FT, Wenning C, Rahbar K, Schober O Schäfers M. Nuclear medicine imaging of the heart and large vessels - State of the art. Zeitschrift für Herz-, Thorax- und Gefäßchirurgie 2010;24: 169-184. Abstract
Schäfers M, Schober O, Hermann S. Matrix-metalloproteinases as imaging targets for inflammatory activity in atherosclerotic plaques. J Nucl Med 2010;51: 663-666. Abstract

Team

Teilprojektleiter

Sven Hermann

Dr. med. Sven Hermann
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49303
hermann.sven@uni-muenster.de

Univ.-Prof. Dr. med. Bodo Levkau
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49300
bodo.levkau@uni-due.de

Michael Schäfers

Univ.-Prof. Dr. med. Michael Schäfers
Klinik für Nuklearmedizin
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49300
schafmi@uni-muenster.de

Wissenschaftliche Mitarbeiter

Dr. rer. nat. Lisa Honold
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49309
lisa.honold@uni-muenster.de

Katrin Schwegmann

Dr. rer. nat. Katrin Schwegmann
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49309
k.schwegmann@uni-muenster.de

Robert Seifert cand. med.
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49300
robert.seifert@uni-muenster.de

Vranchimis-a2

Dr. med. Alexis Vrachimis
Klinik für Nuklearmedizin
Tel.: +49 251 83-47362

Xing-Xin

Dr. rer. nat. Xin Xing
European Institute for Molecular Imaging (EIMI)
Tel.: +49 251 83-49334
xinx@uni-muenster.de

Nicht-wissenschaftliche Mitarbeiter

Christine Bätza

Christine Bätza
European Institute for Molecular Imaging (EIMI)
Medizinisch-technische Assistentin
Tel.: +49 251 83-49306

Hoppe-i

Irmgard Hoppe
European Institute for Molecular Imaging (EIMI)
Medizinisch-technische Assistentin
Tel.: +49 251 83-49307/8

Sarah Köster

Sarah Köster
European Institute for Molecular Imaging (EIMI)
Biologisch-technische Assistentin
Tel.: +49 251 83-49311
sarah.koester@ukmuenster.de


Kontakt

Univ.-Prof. Dr. med. Michael Schäfers
Tel.: +49 251 83-49300
schafmi@uni-muenster.de

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