Probe Design for Molecular Imaging

Molecular imaging refers to the non-invasive visualization of processes taking place at the cellular and molecular level, such as receptor expression and enzyme activity. Various different diagnostic modalities can be used for molecular imaging purposes, including e.g. PET, MRI, OI, and US. The vast majority of molecular imaging techniques rely on the use of contrast agents. Contrast agents suitable for molecular imaging purposes either aim to selectively bind to receptors structures overexpressed at the target site, or to be specifically cleaved by enzymes overexpressed at the target site. Among the contrast agents routinely used for molecular imaging are low-molecular-weight PET- and OI-probes, 1-200 nm-sized MR agents and 1-3 µm-sized US agents. Efforts in our group focus on the design and evaluation of all of these materials. Concerning PET- and MR-tracers, novel metabolic markers for imaging tumors are being tested. In this context, chemical strategies for DOTA-coupling are being explored, and riboflavin analogues, such as FMN and FAD, are being used as adsorptive, non-polymeric and fluorescent coatings for ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles. As part of the Patim/in.NRW project, we also work on the labeling of tissue-engineered cardiovascular grafts with iron oxide- and/or fluor-based MR contrast agents, to enable the non-invasive visualization of scaffold localization, resorption and function. Finally, concerning US, we develop various different types of polymer-based microbubbles for visualizing receptor expression on activated endothelial cells during tumor angiogenesis and atherosclerosis, including e.g. integrins, selectins and CAM’s.

 

Selected publications

Research Papers
  1. Jayapaul J, Hodenius M, Arns S, Lederle W, Lammers T, Comba P, Kiessling F, and Gaetjens J. FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells. Biomaterials. 2011;32(25):5863‑71.
  1. Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F, and Gätjens J. Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging. Biomaterials. 2011;32(26):6155‑63.
  1. Hodenius M, Würth C, Jayapaul J, Wong JE, Lammers T, Gätjens J, Arns S, Mertens N, Slabu I, Ivanova G, Bornemann J, Cuyper MD, Resch-Genger U, and Kiessling F. Fluorescent magnetoliposomes as a platform technology for functional and molecular MR and optical imaging. Contrast Media Mol Imaging. 2012;7(1):59‑67.
  1. Fokong S, Theek B, Wu Z, Koczera P, Appold L, Jorge S, Resch-Genger U, van Zandvoort M, Storm G, Kiessling F, and Lammers T. Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles. J Control Release. 2012;163(1):75‑81.
  1. Jayapaul J, Arns S, Lederle W, Lammers T, Comba P, Gätjens J, and Kiessling F. Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors. Biomaterials. 2012;33(34):8822‑9.

 

Reviews / Perspectives

  1. Kiessling F, Huppert J, and Palmowski M. Functional and molecular ultrasound imaging: concepts and contrast agents. Curr Med Chem. 2009;16(5):627‑42.
  1. Kiessling F, Gaetjens J, and Palmowski M. Application of molecular ultrasound for imaging integrin expression. Theranostics. 2011;1:127‑34.
  1. Kiessling F, Bzyl J, Fokong S, Siepmann M, Schmitz G, and Palmowski M. Targeted ultrasound imaging of cancer: an emerging technology on its way to clinics. Curr Pharm Des. 2012;18(15):2184‑99.
  1. Kiessling F, Fokong S, Koczera P, Lederle W, and Lammers T. Ultrasound microbubbles for molecular diagnosis, therapy, and theranostics. J Nucl Med. 2012;53(3):345‑8.
  1. Kiessling F. Science to practice: genetic engineering meets cell tracking--a promising approach for cell-based therapies? Radiology. 2012;265(1):1‑3.

Group members

Lia (B.Sc. Chemistry, RWTH Aachen, 2012) works on the synthesis and characterization of model drug-loaded MB. She furthermore develops strategies and analytical techniques to PEGylate MB, and to accurately quantify the degree of surface functionalization, PEGylation and drug loading.

Christoph (Biotechnology Master student, RWTH) evaluates different peptides as possible ligands for vascular targeting. In addition, he develops a method for specific gas and drug loading of PBCA microbubbles.

Stanley (MSc in Biomedical Engineering, FH Aachen, 2010) develops polymer-based MB for monitoring tumor angiogenesis and for tumor-targeted drug delivery. He not only optimizes the physicochemical properties of the MB for imaging purposes, but also establishes (physico-) chemical methods to enable their functionalization with antibodies and peptides. Furthermore, he works on strategies to load MB with fluorophores, drugs and imaging agents, and to visualize and quantify their release upon US-mediated MB destruction.

Felix (Dipl.-Chem., Bergische Universität Wuppertal, 2009) synthesizes and characterizes complexes for chelating radonuclides and MR contrast agents into protein- and peptide-based diagnostics. In addition, he is involved in projects focusing on the generation of DOTA-containing low-molecular-weight radiotracers for flavin-based metabolic PET imaging.

Nihan (B.Sc. in Chemical Engineering, Hacettepe University, 2008; M.Sc. in Bioengineering, Hacettepe University, 2011) works on multifunctional complexes to bind with hydrogel carriers for ex-vivo or soft-tissue targets and develops 3D visibility in MRI and CT hybrids. She is currently a Marie Curie fellow of iTERM Project (Nano4Imaging GmbH, Aachen).

Fabian (B.Sc. Physics, TU Darmstadt) works on his thesis for achieving a master’s degree in Biomedical Engineering (RWTH Aachen). His research centers on the use of 19F chemicals as MRI imaging agents. To gain insight about the possibilities of fluorine imaging detection limits are determined and sequence parameters optimized. As a practical application cell labeling experiments are undertaken.

Marianne (MSc in Biotechnology, RWTH Aachen University, 2009) investigates the imaging of patient-customized, tissue-engineered implants. Her work includes the integration of iron oxide-based MR contrast agents into cardiovascular implants, to enable the non-invasive visualization of their localization, resorption and function. To this end, as part of the PatIm Project (Innovating Medical Technology in.nrw), she uses both passive and active (physico-) chemical means to label 2D and 3D collagen scaffolds and PLA-based textile structures with USPIO nanoparticles. In addition, she develops and tests fluorine-containing nanoparticles and polymeric linker molecules for visualizing cardiovascular implants using 19F-MRI.

Yoanna (Dipl.-Chem., RWTH Aachen, 2011) develops adsorptive and fluorescent coatings for USPIO-based nanoparticles for MR, NIRF and PET/SPECT imaging. In this regard she particularly focuses on riboflavin and its analogues, FMN and FAD.

Marek works as a technician in the Probe Design for Molecular Imaging group. He assists MSc and PhD students in the synthesis and characterization of (antibody-targeted) MB, PLGA-based nanoparticles USPIO and MR/PET-probes. He is also responsible for HPLC- and GC-based analyses.