Project P6
Molecular imaging of tissue remodeling in CKD
Dr. rer. nat. Barbara M. Klinkhammer
Institute of Pathology
Department of Nephrology
University hospital RWTH Aachen
E-Mail: bklinkhammer@ukaachen.de
Univ.-Prof. Dr. Dr. Twan Lammers
Department of Nanomedicine &Theranostics
Institute for Experimental Molecular Imaging
Center for Biohybrid Medical Systems
RWTH Aachen University
E-Mail: tlammers@ukaachen.de
Department of Nanomedicine &Theranostics
Institute for Experimental Molecular Imaging
Univ.-Prof. Dr. med. Felix M. Mottaghy
Department of Nuclear medicine
University hospital RWTH Aachen
E-Mail: fmottaghy@ukaachen.de
The lack of specific and non-invasive biomarkers for diagnosis, staging and treatment monitoring of chronic kidney disease (CKD) has hampered the translation of novel drugs from preclinical settings into clinical practice. Histopathological analysis of kidney biopsies is the only available means to specifically assess the extent of renal fibrosis, but it only provides information on a small fraction of the kidney and due to their invasiveness cannot be repeated frequently and hence longitudinal monitoring is impossible. Using elastin-specific magnetic resonance imaging and collagen-specific optical imaging, we recently provided proof-of-concept for the non-invasive and quantitative assessment of whole organ kidney fibrosis stage, progression and anti-fibrotic treatment efficacy.
In the present project, we develop fibrosis-specific molecular imaging probes and protocols to non-invasively visualize and quantify renal fibrosis. We will focus on radionuclide-labeled probes for SPECT and on protocols that allow for direct translation to patients. Among the key objectives is the establishment of molecular imaging setups enabling the simultaneous assessment of both the ECM components and the cells that produce them, which can be achieved by labeling our probes with radionuclides displaying distinct emission spectra. Together, the probes and protocols developed in this project will contribute to the generation of novel disease-specific surrogate end-points, which will facilitate clinical drug testing and translational research and improve patient management in CKD.
Conen P, Pennetta F, Dendl K, Hertel F, Vogg A, Haberkorn U, Giesel FL, Mottaghy FM. [68 Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease. Eur J Nucl Med Mol Imaging. 2022 Jan 6. doi: 10.1007/s00259-021-05660-1. Epub ahead of print. PMID: 34988624
Baues M*, Klinkhammer BM*, Ehling J, Gremse F, van Zandvoort MAMJ, Reutelingsperger CPM, Daniel C, Amann K, Bábíčková J, Kiessling F, Floege J, Lammers T, Boor P. A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo. Kidney Int 2020 Mar;97(3):609-614. (*,’ equal contribution)
Wolf F, Paefgen V, Winz O, Mertens M, Koch S, Gross-Weege N, Morgenroth A, Rix A, Schnoering H, Chalabi K, Jockenhoevel S, Lammers T, Mottaghy F’, Kiessling F, Mela P. MR and PET-CT monitoring of tissueengineered vascular grafts in the ovine carotid artery. Biomaterials 2019, 216:119228. (’ equal contribution)
Sun Q*, Baues M*, Klinkhammer BM*, Ehling J, Djudjaj S, Drude N, Daniel C, Amann K, Kramann R, Kim H, Saez-Rodriguez J, Weiskirchen R, Onthank D, Botnar R, Kiessling F, Floege J, Lammers T, Boor P. Elastin imaging enables non-invasive staging and treatment monitoring of kidney fibrosis. Sci Transl Med 2019, 11: eaat4865. (*,’ equal contribution)
Baues M, Dasgupta A, Ehling J, Prakash J, Boor P, Tacke F, Kiessling F, Lammers T. Fibrosis imaging: Current concepts and future directions. Adv Drug Deliv Rev 2017; 121:9-26
Selected Publications