Molecular imaging of the alveolar echinococcosis in small animals

• Applicant: Dr. Stefan Wiehr
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Medical Physics, Biomedical Technology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195043480

• Final Report Year: 2018

Final Report Abstract

The rapid, non-invasive and highly specific diagnosis of infectious diseases is still challenging, although novel techniques from the field of radiology and nuclear medicine have been implemented. During the funding period the development of pathogen-specific antibody-based PET tracers for the molecular imaging of the severe infectious disease, the parasitic zoonosis alveolar echinococcosis, was performed. Standard clinical PET tracers (e.g. [18F]FDG, [18F]FLT etc.) were evaluated in animal model the diseases in order to extend the diagnostic armamentarium for clinicians. However, standard PET tracers, especially [18F]FDG, revealed to lack specificity being unable to discriminate between sterile and pathogen-induced inflammation and infectious diseases as it is taken up by highly proliferating immune cells frequently infiltrating the site of infection. The E. multilocularis-specific mAb MAbG11 was radiolabeled with 64Cu for the molecular imaging of AE in immunoPET. The tracers showed excellent potential for the highly specific detection of the pathogen in vivo. [64Cu]DOTA- MAbG11 or its 89Zr-labeled variant revealed highly specific binding to E. multilocularis in vitro, and in part in vivo, whereas binding characteristics of this PET tracer need to be further improved and specificity has to be verified in additional control studies using various other pathogens. The findings presented here show the high potential of immunoPET for the rapid, non-invasive, and highly specific diagnosis of infectious diseases. The high potential for the clinical translation of the antibody-based PET tracer was confirmed as it could provide improved diagnosis and staging of the infectious disease in patients as well as beneficial effects on therapy planning and monitoring of the response to antiparasitic treatment.

Publications

• (2014). "Preclinical and Translational PET/MR Imaging." J Nucl Med 55(Supplement 2): 11S-18S
  Wehrl, H. F., S. Wiehr, M. R. Divine, S. Gatidis, G. T. Gullberg, F. C. Maier, A. M. Rolle, J. Schwenck, W. M. Thaiss and B. J. Pichler
  
• (2015). "Evaluation of the Metabolic Activity of Echinococcus multilocularis in Rodents Using Positron Emission Tomography Tracers." Mol Imaging Biol 17(4): 512-520
  Rolle, A. M., P. T. Soboslay, G. Reischl, W. H. Hoffmann, B. J. Pichler and S. Wiehr
  
• (2016). "Fluorescence and Cerenkov luminescence imaging. Applications in small animal research." Nuklearmedizin 55(2): 63-70
  Schwenck, J., K. Fuchs, S. H. Eilenberger, A. M. Rolle, S. Castaneda Vega, W. M. Thaiss and F. C. Maier
  
• (2016). "ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo." Proc Natl Acad Sci USA 113(8): E1026-1033
  Rolle, A. M., M. Hasenberg, C. R. Thornton, D. Solouk-Saran, L. Mann, J. Weski, A. Maurer, E. Fischer, P. R. Spycher, R. Schibli, F. Boschetti, S. Stegemann-Koniszewski, D. Bruder, G. W. Severin, S. E. Autenrieth, S. Krappmann, G. Davies, B. J. Pichler, M. Gunzer and S. Wiehr
  
• (2016). "New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection." Oncotarget 7(10): 10990-11001
  Wiehr, S., P. Warnke, A. M. Rolle, M. Schutz, P. Oberhettinger, U. Kohlhofer, L. Quintanilla- Martinez, A. Maurer, C. Thornton, F. Boschetti, G. Reischl, I. B. Autenrieth, B. J. Pichler and S. E. Autenrieth
  
• (2016). "The Positron Emission Tomography Tracer 3'- Deoxy-3'-[18F]fzluorothymidine ([18F]FLT) Is Not Suitable to Detect Tissue Proliferation Induced by Systemic Yersinia enterocolitica Infection in Mice." PLoS One 11(10): e0164163
  Wiehr, S., A. M. Rolle, P. Warnke, U. Kohlhofer, L. Quintanilla-Martinez, G. Reischl, I. B. Autenrieth, B. J. Pichler and S. E. Autenrieth
  
• (2017) Molecular Imaging of Infectious Diseases. In: Kiessling F., Pichler B., Hauff P. (eds) Small Animal Imaging. Springer, Cham
  Rolle AM., Wiehr S.
  
• (2017). "Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo." Theranostics 7(14): 3398- 3414
  Davies, G., A. M. Rolle, A. Maurer, P. R. Spycher, C. Schillinger, D. Solouk-Saran, M. Hasenberg, J. Weski, J. Fonslet, A. Dubois, F. Boschetti, F. Denat, M. Gunzer, M. Eichner, L. S. Ryder, M. Jensen, R. Schibli, B. J. Pichler, S. Wiehr and C. R. Thornton
  
• (2017). Fungal Imaging. In: Jain, Sanjay K. (Ed.). Imaging Infections - From Bench to Bedside. Springer International Publishing AG
  Greetje Vande Velde and Stefan Wiehr
  
• The effects of taxanes, vorinostat and doxorubicin on growth and proliferation of Echinococcus multilocularis metacestodes assessed with magnetic resonance imaging and simultaneous positron emission tomography, Oncotarget 2018
  Xiangsheng Huang, Stefan Wiehr, Anna-Maria Rolle, Wolfgang Hoffmann, Beate Grüner, Carsten Köhler, Peter T. Soboslay