Radionuclide Molecular Imaging

Objectives

Long term goals: 
We are implementing a translational molecular imaging environment, which facilitates 

  • Effective guidance of clinical regenerative therapies based on image-defined individual disease biology
  • Hand-in-hand development of novel imaging techniques and novel therapies, from basic science to clinical application 

In the near future we aim:

  • To further expand our radionuclide imaging toolbox for in vivo phenotyping of experimental animals and human subjects in various disease states and in response to regenerative therapy. 
  • To translate algorithms for noninvasive tracking of the location, fate, viability and functional effects of therapeutic targets and vehicles (genes, cells, bioimplants) from experimental animals to human application. 
  • To grow our interdisciplinary, multi-modality framework for research, practical application, and education in molecular imaging in regenerative sciences. 

Milestones: 

  • Development of novel imaging probes for cell adhesion, cell/matrix interaction, inflammation and fibrosis  
  • In vivo phenotyping of transgenic animals and disease models using imaging markers of inflammation, metabolism, receptors and extracellular matrix activation 
  • Development of reporter gene-based imaging techniques for tracking of endogenous cell trafficking 

Research Focus

Radiotracer-based molecular imaging provides unique opportunities in regenerative medicine. Key biologic mechanisms such as inflammation, metabolism, and protein/receptor interaction can be interrogated in vivo, by noninvasive means. Additionally, therapeutic agents such as cells, genes and proteins can be labelled and tracked. Using hybrid technology, the tracer-derived molecular information can be fused with high-resolution morphologic information from X-ray CT, for accurate localization. This provides (1) detailed insights into disease mechanisms and biologic precursors of overt disease (which may facilitate early detection and prevention), (2) characterization of the individual phenotype (which may be a powerful predictor of response to specific interventions), (3) definition of inter-organ interaction and networking by whole-body imaigng and (4) identification of early effects of novel therapies (which may be a surrogate for subsequent long-term benefit). Another unique feature is that radionuclide imaging can be employed in small experimental animals, large animals and humans, thereby facilitating translation from initial development to clinical application. 

The radionuclide molecular imaging group of REBIRTH 2 aims at the establishment, growth and practical implementation of a translational toolbox for imaging of regeneration. This includes preclinical and clinical testing of newly developed markers of inflammation and cell-cell or cell-matrix interaction, and it tailors existing techniques such as reporter gene approaches and cell tracking to the needs of specific research questions of the consortium. 

A major focus will be the development of robust techniques for characterization of the early wound healing phase after acute myocardial infarction and for quantification of the effect of molecular interventions targeting infarct repair. Another focus will be on methods for tracking endogenous bone marrow progenitor cells and their pathways in inflammatory and regenerative processes. 

Ultimately, specific projects of the research unit will lead to broader application in related settings of the REBIRTH 2 consortium, with the vision of establishing new molecular imaging tests that guide regenerative therapies towards initial clinical application and in subsequent patient care. 

Collaborations

  • Prof. Dr. Kai Wollert, REBIRTH Unit Secreted Factors and non-cell-based Strategies for Cardiac Repair, Molecular and Translational Cardiology, MHH (Imaging of post-infarct inflammation and myocardial recruitment of bone marrow progenitor cell) 
  • Prof. Dr. Denise Hilfiker-Kleiner, REBIRTH Unit Endogenous Regeneration Mechanismsof the Heart, Molecular Cardiology, MHH (Phenotying of mouse models of heart failure) 
  • Prof. Dr. Andre Bleich, Dr. Martin Meier, REBIRTH Unit Small Animal MRI, Laboratory Animal Research, MHH (Multi-modality imaging of small animal models) 
  • Prof. Frank Wacker, REBIRTH Unit Functional and Molecular MRI, Diagnostic and Interventional Radiology, MHH (Multi-modality imaging of large animal models) 
  • Prof. Dr. Matthias Ochs, Prof. Dr. Christian Mühlfeld, REBIRTH Unit Quantitative microscopy in Regeneration, Anatomy, MHH (Integrated in vivo/ex vivo analysis of myocardial neuronal regeneration)
  • Juhani Knuuti, MD, University PET Center, Turku, Finland (In vivo phenotyping of metabolic heart disease; molecular probe development) 
  • Prof. Dr. Hans-Jürgen Wester, Radiopharmaceutical Chemistry, Technical University of Munich, Germany

Publications

2013 - ongoing

2018

Thackeray JT, Hupe HC, Wang Y, Bankstahl JP, Berding G, Ross TL, Bauersachs J, Wollert KC, Bengel FM. Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction. Journal of the American College of Cardiology. 2018;71(3):263-75.

Thackeray JT, Bengel FM. Gauging cardiac repair and regeneration with new molecular probes. Journal of Nuclear Medicine. 2018.

2017

Sohns JM, Bavendiek U, Ross TL, Bengel FM. Targeting Cardiovascular Implant Infection. Circulation: Cardiovascular Imaging. 2017;10(12).

Weiberg D, Thackeray JT, Daum G, Sohns JM, Kropf S, Wester HJ, Ross TL, Bengel FM, Derlin T. Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque using (68)Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden. J Nucl Med. 2017/08/05 ed2017.

Bengel FM. Issue "noninvasive molecular imaging and theranostic probes": New concepts in myocardial imaging. Methods. 2017/06/04.

Thackeray JT, Pietzsch S, Stapel B, Ricke-Hoch M, Lee CW, Bankstahl JP, Scherr M, Heineke J, Scharf G, Haghikia A, Bengel FM, Hilfiker-Kleiner D. Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression. JCI Insight. 2017/05/19 ed2017.

Derlin T, Gueler F, Brasen JH, Schmitz J, Hartung D, Herrmann TR, Ross TL, Wacker F, Wester HJ, Hiss M, Haller H, Bengel FM, Hueper K. Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney Transplantation. J Nucl Med. 2017/04/30 ed2017. p. 1831-7.

Ernst D, Weiberg D, Baerlecken NT, Schlumberger W, Daehnrich C, Schmidt RE, Bengel FM, Derlin T, Witte T. Anti-MYC-associated zinc finger protein antibodies are associated with inflammatory atherosclerotic lesions on (18)F-fluorodeoxyglucose positron emission tomography. Atherosclerosis. 2017/03/11 ed2017. p. 12-9.

2016

Derlin T, Thiele J, Weiberg D, Thackeray JT, Puschel K, Wester HJ, Aguirre Davila L, Larena-Avellaneda A, Daum G, Bengel FM, Schumacher U. Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization. Arterioscler Thromb Vasc Biol. 2016/10/28 ed2016. p. 2213-9.

Thackeray JT, Bengel FM. Specificity vs versatility: A fine balance for novel targeted molecular imaging radiotracers. J Nucl Cardiol. 2016.

Thackeray JT, Bengel FM. PET imaging of the autonomic nervous system. Q J Nucl Med Mol Imaging. 2016;60(4):362-82.

Thackeray JT, Bengel FM. Translational Molecular Nuclear Cardiology. Cardiol Clin. 2016;34(1):187-98.

Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction. Theranostics. 2016;6(11):1768-79.

Stapel B, Kohlhaas M, Ricke-Hoch M, Haghikia A, Erschow S, Knuuti J, Silvola JM, Roivainen A, Saraste A, Nickel AG, Saar JA, Sieve I, Pietzsch S, Muller M, Bogeski I, Kappl R, Jauhiainen M, Thackeray JT, Scherr M, Bengel FM, Hagl C, Tudorache I, Bauersachs J, Maack C, Hilfiker-Kleiner D. Low STAT3 expression sensitizes to toxic effects of beta-adrenergic receptor stimulation in peripartum cardiomyopathy. European heart journal. 2016.

Caobelli F, Wollenweber T, Bavendiek U, Kuhn C, Schutze C, Geworski L, Thackeray JT, Bauersachs J, Haverich A, Bengel FM. Simultaneous dual-isotope solid-state detector SPECT for improved tracking of white blood cells in suspected endocarditis. European heart journal. 2016.

Bengel FM. The Role of Attractiveness: Imaging the Interaction Between Cardiovascular and Immune System. J Nucl Med. 2016;57(7):1004-5.

Bengel FM. Imaging of Post-Infarct Inflammation: Moving Forward Toward Clinical Application. Circ Cardiovasc Imaging. 2016;9(4):e004713.

2015

Thackeray JT, Derlin T, Haghikia A, Napp LC, Wang Y, Ross TL, Schäfer A, Tillmanns J, Wester HJ, Wollert KC, Bauersachs J, Bengel FM. Molecular Imaging of the Chemokine Receptor Cxcr4 after Acute Myocardial Infarction. JACC: Cardiovascular Imaging. 2015.

Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically Relevant Strategies for Lowering Cardiomyocyte Glucose Uptake for 18f-Fdg Imaging of Myocardial Inflammation in Mice. Eur J Nucl Med Mol Imaging. 2015;42(5):771-80.

Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, Wollert KC, Bengel FM. Targeting Post-Infarct Inflammation by Pet Imaging: Comparison of Ga-68-Citrate and Ga-68-Dotatate with F-18-Fdg in a Mouse Model. European Journal of Nuclear Medicine and Molecular Imaging. 2015;42(2):317-27.

Thackeray JT, Bankstahl JP, Bengel FM. Impact of Image-Derived Input Function and Fit Time Intervals on Patlak Quantification of Myocardial Glucose Uptake in Mice. J Nucl Med. 2015;56(10):1615-21.

Li XG, Roivainen A, Bergman J, Heinonen A, Bengel F, Thum T, Knuuti J. Enabling [(18)F]-Bicyclo[6.1.0]Nonyne for Oligonucleotide Conjugation for Positron Emission Tomography Applications: [(18)F]-Anti-Microrna-21 as an Example. Chem Commun (Camb). 2015;51(48):9821-4.

Lautamaki R, Sasano T, Higuchi T, Nekolla SG, Lardo AC, Holt DP, Dannals RF, Abraham MR, Bengel FM. Multiparametric Molecular Imaging Provides Mechanistic Insights into Sympathetic Innervation Impairment in the Viable Infarct Border Zone. J Nucl Med. 2015;56(3):457-63. Epub 2015/01/31.

Derlin T, Janssen T, Salamon J, Veldhoen S, Busch JD, Schon G, Herrmann J, Henes FO, Bannas P, Adam G. Age-Related Differences in the Activity of Arterial Mineral Deposition and Regional Bone Metabolism: A 18f-Sodium Fluoride Positron Emission Tomography Study. Osteoporos Int. 2015;26(1):199-207.

Caobelli F, Bengel FM. Ischaemic Vs Non-Ischaemic Dilated Cardiomyopathy: The Value of Nuclear Cardiology Techniques. J Nucl Cardiol. 2015;22(5):971-4.

Caobelli F, Bengel FM. In Vivo Evaluation of Atherosclerotic Plaques and Culprit Lesions Using Noninvasive Techniques. Nat Rev Cardiol. 2015;12(2):79-.

Bravo PE, Lautamaki R, Carter D, Holt DP, Nekolla SG, Dannals RF, Russell SD, Bengel FM. Mechanistic Insights into Sympathetic Neuronal Regeneration: Multitracer Molecular Imaging of Catecholamine Handling after Cardiac Transplantation. Circ Cardiovasc Imaging. 2015;8(8):e003507. Epub 2015/08/08.

Derlin T, Alchalby H, Bannas P, Veldhoen S, Apostolova I, Triviai I, Bengel FM, Kroger N. Assessment of Bone Marrow Inflammation in Patients with Myelofibrosis: An 18f-Fluorodeoxyglucose Pet/Ct Study. Eur J Nucl Med Mol Imaging. 2015;42(5):696-705.

2014

Wollenweber T, Roentgen P, Schafer A, Schatka I, Zwadlo C, Brunkhorst T, Berding G, Bauersachs J, Bengel FM. Characterizing the Inflammatory Tissue Response to Acute Myocardial Infarction by Clinical Multimodality Noninvasive Imaging. Circ Cardiovasc Imaging. 2014;7(5):811-8.

Wollenweber T, Bengel FM. Cardiac Molecular Imaging. Semin Nucl Med. 2014;44(5):386-97.

Thackeray JT, deKemp RA, Beanlands RS, DaSilva JN. Early Diabetes Treatment Does Not Prevent Sympathetic Dysinnervation in the Streptozotocin Diabetic Rat Heart. J Nucl Cardiol. 2014;21(4):829-41. Epub 2014/06/04.

Stockhofe K, Postema JM, Schieferstein H, Ross TL. Radiolabeling of Nanoparticles and Polymers for Pet Imaging. Pharmaceuticals (Basel). 2014;7(4):392-418.

Schieferstein H, Kelsch A, Reibel A, Koynov K, Barz M, Buchholz HG, Bausbacher N, Thews O, Zentel R, Ross TL. 18f-Radiolabeling, Preliminary Evaluation of Folate-Phpma Conjugates Via Pet. Macromol Biosci. 2014;14(10):1396-405.

Schatka I, Bengel FM. Advanced Imaging of Cardiac Sarcoidosis. J Nucl Med. 2014;55(1):99-106.

Knuuti J, Bengel F, Bax JJ, Kaufmann PA, Le Guludec D, Perrone Filardi P, Marcassa C, Ajmone Marsan N, Achenbach S, Kitsiou A, Flotats A, Eeckhout E, Minn H, Hesse B. Risks and Benefits of Cardiac Imaging: An Analysis of Risks Related to Imaging for Coronary Artery Disease. Eur Heart J. 2014;35(10):633-8.

Happle C, Lachmann N, Skuljec J, Wetzke M, Ackermann M, Brennig S, Mucci A, Jirmo AC, Groos S, Mirenska A, Hennig C, Rodt T, Bankstahl JP, Schwerk N, Moritz T, Hansen G. Pulmonary Transplantation of Macrophage Progenitors as Effective and Long-Lasting Therapy for Hereditary Pulmonary Alveolar Proteinosis. Sci Transl Med. 2014;6(250):250ra113.

Bengel FM, Thackeray JT. Altered Cardiac Innervation Predisposes to Ventricular Arrhythmia: Targeted Positron Emission Tomography Identifies Risk in Ischemic Cardiomyopathy. J Am Coll Cardiol. 2014;63(2):150-2.

Bengel FM. The Non-Invasive Biopsy: Molecular Imaging for the Detection of Cardiac Involvement in Systemic Disease. Eur Heart J Cardiovasc Imaging. 2014;15(11):1299-300.

Bankstahl JP. What Does a Picture Tell? In Vivo Imaging of Abc Transporter Function. Drug Discov Today Technol. 2014;12:e113-9. Epub 2014/07/17.

2013

Thackeray JT, deKemp RA, Beanlands RS, DaSilva JN. Insulin Restores Myocardial Presynaptic Sympathetic Neuronal Integrity in Insulin-Resistant Diabetic Rats. J Nucl Cardiol. 2013;20(5):845-56.

Thackeray JT, Bengel FM. Assessment of Cardiac Autonomic Neuronal Function Using Pet Imaging. J Nucl Cardiol. 2013;20(1):150-65.

Schatka I, Wollenweber T, Haense C, Brunz F, Gratz KF, Bengel FM. Peptide Receptor-Targeted Radionuclide Therapy Alters Inflammation in Atherosclerotic Plaques. J Am Coll Cardiol. 2013;62(24):2344-5.

Janssen T, Bannas P, Herrmann J, Veldhoen S, Busch JD, Treszl A, Munster S, Mester J, Derlin T. Association of Linear (1)(8)F-Sodium Fluoride Accumulation in Femoral Arteries as a Measure of Diffuse Calcification with Cardiovascular Risk Factors: A Pet/Ct Study. J Nucl Cardiol. 2013;20(4):569-77. Epub 2013/04/17.

Higuchi T, Rischpler C, Fukushima K, Isoda T, Xia J, Javadi MS, Szabo Z, Dannals RF, Mathews WB, Bengel FM. Targeting of Endothelin Receptors in the Healthy and Infarcted Rat Heart Using the Pet Tracer 18f-Fbzbms. J Nucl Med. 2013;54(2):277-82.

Bengel FM, George RT, Schuleri KH, Lardo AC, Wollert KC. Image-Guided Therapies for Myocardial Repair: Concepts and Practical Implementation. Eur Heart J Cardiovasc Imaging. 2013;14(8):741-51.

2006 - 2012

2012

Fukushima K, Bravo PE, Higuchi T, Schuleri KH, Lin X, Abraham MR, Xia J, Mathews WB, Dannals RF, Lardo AC, Szabo Z, Bengel FM. Molecular Hybrid Positron Emission Tomography/Computed Tomography Imaging of Cardiac Angiotensin Ii Type 1 Receptors. J Am Coll Cardiol. 2012;60(24):2527-34.

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