2011 - ExMI – Experimental Molecular Imaging - RWTH
2011 - ExMI – Experimental Molecular Imaging - RWTH
2011 - ExMI – Experimental Molecular Imaging - RWTH
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Chair of <strong>Experimental</strong> <strong>Molecular</strong> <strong>Imaging</strong><br />
Faculty of Medicine<br />
<strong>Imaging</strong><br />
Pathophysiology<br />
Down to the<br />
<strong>Molecular</strong> Level<br />
Director<br />
Univ.-Prof. Dr. med. Fabian Kießling<br />
<strong>RWTH</strong> Aachen University Hospital<br />
Pauwelsstrasse 30, D-52074 Aachen<br />
Helmholtz-Institute for Biomedical Engineering<br />
Pauwelsstrasse 20, D-52074 Aachen<br />
Phone: +49 (0)241 80 80116 (Secretary)<br />
+49 (0)241 80 80117 (Office)<br />
Fax: +49 (0)241 80 33 80116<br />
Email: fkiessling@ukaachen.de<br />
Web: http://www.molecular-imaging.ukaachen.de<br />
Staff<br />
Abou-Elkacem, Lotfi, Dipl.-Biol, PhD student<br />
Al Rawashdeh, Wa’el, MSc, PhD student<br />
Appold, Lia, BSc student<br />
Arns, Susanne, Technical assistant<br />
Bätke, Sarah, MSc, PhD student<br />
Berker, Yannick, Dipl.-Ing. MSc, PhD student<br />
Bölükbas, Ali, MSc student<br />
Bzyl, Jessica, BSc, PhD student<br />
Curaj, Adelina, MD, PhD student<br />
Doleschel, Dennis, Dipl.-Biol, PhD student<br />
Duarte Jorge, Samuel, MSc student<br />
Dueppenbecker, Peter, Dipl.-Ing., PhD student<br />
Ehling, Josef, Dr. med., Postdoc<br />
Fokong, Stanley, MSc, PhD student<br />
Franke, Jochen, MSc student<br />
Fuge, Felix, Dipl.-Chem, PhD student<br />
Gätjens, Jessica, Dr. rer. nat., Group leader<br />
Gebhardt, Pierre, Dipl.-Ing., PhD student<br />
Goldschmidt, Benjamin, Dipl.-Ing., PhD student<br />
Gremse, Felix, Dipl.-Ing., PhD student<br />
Grouls, Christoph, MD Student<br />
Jayapaul, Jabadurai, MSc, PhD student<br />
Koczera, Patrick, MD student<br />
Kunjachan, Sijumon, MSc, PhD Student<br />
Lammers, Twan, PhD, DSc, Group leader<br />
Lederle, Wiltrud, Dr. rer. nat., Group leader<br />
Liu, Zhe, PhD, Postdoc<br />
Mertens, Marianne, MSc, PhD student<br />
Mertens, Natascha, Technical assistant<br />
<strong>2011</strong><br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
Möckel, Diana, Technical assistant<br />
Novak, Mara, Technical assistant<br />
Palmowski, Karin, Dr. med., Postdoc<br />
Palmowski, Moritz, PD Dr. med., Group leader<br />
Rix, Anne, Technical Assistant<br />
Salomon, Andre, Dr.-Ing., Postdoc<br />
Schultz, Volkmar, Dr.-ing., Group leader<br />
Theek, Benjamin, MSc, student<br />
Tiemann, Birgit, Administrative assistant<br />
Truhn, Daniel, Dipl.-Phys., MSc, PhD student<br />
Weiler, Marek, Technical Assistant<br />
Weissler, Bjoern, Dipl.-Ing., PhD Student<br />
Wu, Zhuojun, MSc, PhD student<br />
Yokota Rizzo, Larissa, MSc, PhD student<br />
35
<strong>Experimental</strong> <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
36<br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
Introduction<br />
The Chair of <strong>Experimental</strong> <strong>Molecular</strong> <strong>Imaging</strong> (<strong>ExMI</strong>) at the<br />
Helmholtz-Institute for Biomedical Engineering (HIA) at<br />
<strong>RWTH</strong> Aachen University focuses on the development and<br />
evaluation of novel imaging methods and contrast agents<br />
to characterize and treat cancer and cardiovascular disorders.<br />
This is mainly achieved by vascular targeting and<br />
theranostic approaches, which are developed and tested in<br />
preclinical animal models. In this context, novel biomaterials,<br />
including nanoparticles, polymeric carriers, liposomes<br />
and microbubbles can play a major role. Their delivery and<br />
therapeutic efficacy can be assessed by functional and molecular<br />
imaging, which has become an established tool in<br />
preclinical research.<br />
<strong>ExMI</strong> follows a multimodal approach, based on combinations<br />
of MRI, CT, ultrasound, optical imaging and nuclear<br />
medicine techniques. Image fusion, hybrid imaging as well<br />
as multimodal contrast agents are in the research scope.<br />
Usually, the choice of imaging strategies and contrast agents<br />
follows the biological and medical problem to be investigated.<br />
Furthermore, we intend to better connect preclinical<br />
and clinical research, and to translate novel surrogate markers<br />
and (molecular) diagnostics into clinical evaluation.<br />
Currently, the department consists of five research groups,<br />
working on the biological mechanisms of tumor development<br />
and angiogenesis, on the synthesis of novel imaging<br />
probes, on theranostic concepts to treat cancer and cardiovascular<br />
diseases, on MR-PET hybrid imaging, and on translational<br />
studies to bring functional and molecular ultrasound<br />
to the clinic.<br />
Mechanisms of Tumor<br />
Progression and Metastasis<br />
The group “Mechanisms of Tumor Progression and<br />
Metastasis” aims at elucidating the mechanisms of tumor<br />
growth and progression, with a special focus on the impact<br />
of the tumor microenvironment and the longitudinal in<br />
vivo characterization by non-invasive imaging. Besides tumor<br />
staging and improved diagnosis, further attempts are<br />
directed to monitor therapy effects, including the evaluation<br />
of novel therapeutics. In vivo imaging is complemented<br />
by histological and functional in vitro analyses in order<br />
to validate the data and to identify new potential markers<br />
and targets.<br />
We recently compared different imaging modalities with<br />
respect to the non-invasive assessment of tumor growth<br />
and size in GFP/RFP-expressing colon carcinoma xenografts.<br />
Magnetic resonance imaging (MRI) was proven to<br />
be highly sensitive and accurate for tumor size and growth<br />
assessment. Micro-computed tomography (µCT) provided<br />
an almost similar accuracy. Optical reflectance imaging<br />
(ORI) was as sensitive as MRI, but overestimated the tumor<br />
size. Fluorescent intensity measurements provided more<br />
accurate data of the tumor size than fluorescent area analyses<br />
(Fig. 1) [1] .<br />
[1] Abou-Elkacem et al, Anticancer Res 31: 2907 (<strong>2011</strong>)<br />
<strong>2011</strong><br />
Fig.1. A: Monitoring of tumor growth in s.c. HCT 116-GFP-<br />
RFP xenografts using ORI, MRI and μCT. Representative<br />
images show tumors at day 1, 3 and 15 after inoculation.<br />
B: Correlation of the tumor volumes determined in vivo by<br />
MRI, μCT and ORI with ex vivo caliper data at day 12 and<br />
15 (n=9). From [1] .<br />
A second study aimed at non-invasive apoptosis assessment<br />
in response to anti-angiogenic therapy, using both<br />
optical imaging (Annexin-Vivo) and gamma counting<br />
( 99m Tc-HYNIC-Annexin V). As opposed to immunohistochemistry,<br />
which clearly showed apoptosis induction<br />
after treatment with the multi-tyrosine kinase inhibitor<br />
SU11248, both Annexin probes were found to be unable<br />
to specifically detect apoptosis in vivo, most probably because<br />
of the breakdown of the vasculature and reduced<br />
probe delivery [2] .<br />
Due to the discovery of the erythropoietin-receptor<br />
(EpoR) on tumor cells, the use of erythropoietin (Epo) for<br />
the treatment of cancer-induced anemia is currently under<br />
intense debate. In order to elucidate the role of Epo<br />
and EpoR in lung cancer, a near-infrared probe for fluorescence<br />
mediated tomography (FMT) was developed and<br />
tested for longitudinally assessing EpoR status in lung cancer<br />
xenografts with different EpoR expression levels. As<br />
shown in Fig. 2, the probe was found to be highly specific,<br />
and could accurately determine the EpoR expression level<br />
of the xenografts in vivo, as demonstrated by FMT/µCT<br />
hybrid imaging. These data suggest a high potential of this<br />
newly developed probe for analyzing the EpoR status in<br />
tumors and the role of Epo in lung cancer [3] .<br />
Fig. 2. Specific binding of Cy5.5-labeled Epo (red) to tumors<br />
with different EpoR expression levels (lower in A549<br />
(A); higher in H838 (B)), as demonstrated via in vivo competition<br />
experiments with excess unlabeled Epo (blue).<br />
FMT/μCT hybrid imaging clearly confirmed the stronger<br />
accumulation of Epo-Cy5.5 in H838 (E) as compared to<br />
A549 (D). White arrows indicate tumors, hatched arrows<br />
bone. From [3] .<br />
[2] Lederle et al, EJNMMI Research 1: 26 (<strong>2011</strong>)<br />
[3] Doleschel et al, J Nucl Med (in press)
Probe Design for <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
The chemical group within <strong>ExMI</strong>, which focuses on the development<br />
of novel probes for molecular imaging, has in<br />
the past year made significant progress towards the development<br />
of FMN- and FAD-coated superparamagnetic iron<br />
oxide (USPIO) nanoparticles, which were shown to be highly<br />
suitable for in vivo imaging of tumors and tumor angiogenesis,<br />
as well as for ex vivo labeling endothelial cells [4] .<br />
In addition, USPIO have been incorporated into poly(butyl<br />
cyanoacrylate)-based microbubbles (MB), thereby enabling<br />
the non-invasive visualization of MB destruction using MRI [5] .<br />
These USPIO-containing MB have furthermore been shown<br />
to be useful for mediating and monitoring drug delivery<br />
across the blood-brain-barrier (BBB). This is exemplified by<br />
Fig. 3, showing the deposition of USPIO nanoparticles released<br />
from MB into the brain upon ultrasound-mediated destruction,<br />
as well as extravasation of the blood pool marker<br />
FITC-dextran from systemic circulation across the BBB [6] .<br />
Fig. 3. Mediating and monitoring blood-brain-barrier<br />
(BBB) permeation using USPIO-containing MB. A-B: T2*relaxation<br />
rates in the brains of mice before (A) and 45<br />
min after (B) the application of USPIO-MB plus destructive<br />
ultrasound (US)<br />
pulses, showing<br />
efficient deposition<br />
of released<br />
USPIO across<br />
the BBB. C-D:<br />
Upon combining<br />
USPIO-MB<br />
with US, significantextravasation<br />
of FITCdextran<br />
(green)<br />
into the brain<br />
was observed<br />
(C), which was<br />
not the case for<br />
non-US-treated<br />
controls (D).<br />
Blood vessels<br />
counterstained<br />
in red.<br />
As part of Patim.NRW, USPIO nanoparticles are also being<br />
developed for visualizing the localization, the resorption and<br />
the functionality of cardiovascular implants, such as stents,<br />
shunts and patches. To this end, as part of an initial proof-ofprinciple<br />
study, collagen-based scaffolds have been prepared<br />
which contain different amounts of USPIO, they have been<br />
characterized using TEM and SEM, cell growth onto and into<br />
these scaffolds has been evaluated, and they have been<br />
used to non-invasively monitor their localization in mice. As<br />
shown in Fig. 4, depending on the amount of USPIO incorporated,<br />
the labeled scaffolds could be visualized with high<br />
sensitivity, both ex vivo and in vivo, and USPIO incorporation<br />
did not affect their structural properties [7] . Experiments<br />
evaluating the impact of USPIO labeling on cell growth and<br />
[4] Jayapaul et al, Biomaterials 32: 5863 (<strong>2011</strong>)<br />
[5] Liu et al, Biomaterials 32: 6155 (<strong>2011</strong>)<br />
[6] Koczera et al (in prep)<br />
[7] Mertens et al (in prep)<br />
<strong>2011</strong><br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
aiming to assess the suitability of these matrices for monitoring<br />
scaffold resorption are currently ongoing.<br />
Fig. 4. USPIO-labeled scaffolds. A-C: Collagen-based matrices<br />
were labeled with different amounts of USPIO (A), and<br />
their structural properties were evaluated using scanning<br />
electron microscopy at 20x (B) and 80x (C) magnification.<br />
D-E: Standard (D) and color-coded (E) T2*-imaging of a<br />
USPIO-labeled scaffold (arrow) upon intraperitoneal implantation.<br />
Nanomedicines and theranostics<br />
Efforts in our group primarily focus on the development of image-guided<br />
nanomedicines for treating cancer and inflammatory<br />
disorders. In the past year, significant progress has been in<br />
the development of passively and actively targeted polymers<br />
and micelles for drug targeting to tumors, as well as in the design<br />
and evaluation of various different nanomedicine formulations<br />
for treating rheumatoid arthritis [8]; [9]; [10] .<br />
In addition, we have evaluated how well nanocarrier materials<br />
are able to overcome multidrug resistance (MDR). To<br />
this end, three different doxorubicin-containing nanomedicines<br />
(i.e. liposomes, polymers and micelles) and four different<br />
cell lines were used (i.e. A431, SW620, B16 and CT26;<br />
both in parental and in MDR-form; obtained upon continuously<br />
exposing the cells to IC90 concentrations, and selecting<br />
surviving cells; see Fig. 5A-B). In line with the literature,<br />
nanomedicines suffered less from the expression of MDRconferring<br />
drug efflux pumps than did free doxorubicin, as<br />
confirmed by both cytotoxicity and cell uptake experiments<br />
(Fig. 5C). As opposed to the literature, however, in which<br />
often pharmacologically active carrier materials and/or artificially<br />
resistant (e.g. Pgp-overexpressing) cells are used, the<br />
differences in IC50 between parental and MDR-cells were<br />
much smaller (2-4; vs. 10-100), indicating that the ability of<br />
clinically relevant nanomedicines to overcome physiologically<br />
relevant MDR should not be overestimated [11] .<br />
Additional experiments in our group, performed as part of<br />
the ForSaTum project, have aimed at imaging and analyzing<br />
[8] Huis in ‘t Veld et al, Nanoscale 3: 4022 (<strong>2011</strong>)<br />
[9] Talleli et al, J Control Release 153: 93 (<strong>2011</strong>)<br />
[10] Crielaard et al (in prep)<br />
[11] Kunjachan et al, Eur J Pharm Sci (in press)<br />
<strong>Experimental</strong> <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
37
<strong>Experimental</strong> <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
38<br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
tumor angiogenesis using a combination of in vivo and ex vivo<br />
micro-computed tomography (µCT) and immunohistochemistry<br />
(IHC). To this end, as exemplified in part by Fig.<br />
6, blood vessels in 4 different subcutaneous xenograft tumors<br />
(A431, Calu-6, MLS and A549) were visualized using<br />
both µCT and IHC, and morphological characteristics such<br />
as vessel size, vessel distribution and vessel branching were<br />
analyzed [12] Fig. 5. Overcoming multidrug-resistance (MDR) using nanomedicines.<br />
A-B: Three different doxorubicin (Dox) -containing<br />
nanomedicine formulations (polymers, liposomes and<br />
micelles; B) were used to evaluate to the impact of drug<br />
targeting on overcoming MDR, hypothesizing that nanomedicines<br />
are more useful than free drugs for achieving target<br />
site (nuclear) localization in vitro (A). C: Fluorescence microscopy<br />
studies, confirming that the upregulation of MDRconferring<br />
drug efflux pumps affects the cellular uptake of<br />
free Dox more strongly than that of Dox-containing nanomedicines.<br />
Dox: red. Nuclei: blue. Cell membranes: green.<br />
. In addition, in vivo µCT imaging<br />
was implemented to non-invasively assess<br />
the relative blood volume (rBV) in these 4<br />
tumors models. Upon comparing the results<br />
obtained using µCT to those obtained<br />
using IHC, which still is the golden standard<br />
in (anti-)angiogenesis experiments, it was<br />
found that the results obtained using both<br />
Fig. 6: Visualization of tumor blood vessels in A549 (A,B,E)<br />
and A431 (C,D,F) tumor xenografts using in vivo (A,C) and<br />
ex vivo (B,D) micro-computed tomography and immunohistochemistry<br />
(E-F). Arrows indicate degree of blood vessel<br />
branching. Blood vessels are stained in green, α-SMA in<br />
red and nuclei in blue.<br />
<strong>2011</strong><br />
experimental procedures correlated very<br />
well, with correlation coefficients far above<br />
0.9 and p-values far below 0.05, indicating that<br />
functional in vivo µCT imaging is a highly suitable<br />
modality for non-invasively evaluating tumor<br />
angiogenesis and the vascular response<br />
to anti-angiogenic therapies.<br />
Hybrid <strong>Imaging</strong><br />
Technologies<br />
New system developments: The group Hybrid <strong>Imaging</strong><br />
Technology (HIT) has developed a new detector concept<br />
for simultaneous Positron Emission Tomography (PET) and<br />
Magnetic Resonance <strong>Imaging</strong> (MRI). The team succeeded in<br />
applying this new detector technology in a preclinical PET/<br />
MR scanner (see Fig. 7). The scanner is designed as an insert<br />
for a human 3T MRI system [13] . The system was designed,<br />
built, and tested within the timeframe of the EU FP7 project<br />
HYPERImage and will be further optimized within the<br />
NRW project ForSaTum. The new MR-compatible detector<br />
stack uses analog and digital Silicon PhotoMultiplier (SiPM)<br />
technology which further advances the performance (sub<br />
nano-second coincidence resolution time) of future semiconductor<br />
based PET system. The detector has been developed<br />
in cooperation with the University of Heidelberg<br />
(Prof. Peter Fischer) and the Fondazione Bruno Kessler<br />
(Claudio Piemonte, PhD). The team has developed a new<br />
data acquisition and control environment for this new generation<br />
of digital PET scanners, which enables a purely SW<br />
based data processing and thus the application of new iterative<br />
algorithms, like self normalization and calibration [14] ,<br />
or maximum likelihood crystal identification to improve the<br />
image resolution and sensitivity [15] . A special gamma-transparent<br />
Radio Frequency (RF) coil supporting simultaneous<br />
PET/MR has been developed for imaging of animals with a<br />
size up to rabbits [16] Fig. 7: Left: simultaneously acquired PET-, MR-, and fused<br />
PET plus MR image. Right: preclinical PET/MR system<br />
. The interference investigation using<br />
the new MR-compatible PET modules finally shows no significant<br />
performance degradation of PET and MRI during simultaneous<br />
acquisition.<br />
MR-based attenuation correction for hybrid PET/MRI systems:<br />
Accurate gamma photon attenuation correction<br />
(AC) is essential for quantitative PET/MRI as there is no<br />
simple relation between MR image intensity and attenuation<br />
coefficients. Attenuation maps (µ-maps) can be<br />
[12] Ehling et al (in prep)<br />
[13] Schulz et al, IEEE NSS, J2-05 (<strong>2011</strong>)<br />
[14] Goldschmidt et al, IEEE NSS, MIC18.M-194 (<strong>2011</strong>)<br />
[15] Lerche et al, IEEE NSS, MIC18.M-180 (<strong>2011</strong>)<br />
[16] Truhn et al, Med Phys 38: 3995 (<strong>2011</strong>)
derived by segmenting MR images and assigning attenuation<br />
values to the compartments. Ultra-short echo time<br />
(UTE) sequences have been used to separate cortical bone<br />
and air, and the Dixon technique has enabled distinguishing<br />
soft and adipose tissues. Unfortunately, sequential application<br />
of these sequences is time-consuming and complicates<br />
image registration. Within the HIT we develop new<br />
MR sequences and mathematical techniques to extract<br />
the attenuation of the gamma photon out of the MR and<br />
the PET data [17] . We recently proposed a UTE triple-echo<br />
(UTILE) MR- sequence [18] Fig. 8: MRI pulse sequence diagram of our UTILE sequence<br />
(left) with image processing flowchart (right)<br />
combining UTE sampling for<br />
bone detection and gradient echoes for Dixon water/fat<br />
separation in a single-shot 3D acquisition (TE1/TE2/TE3/<br />
TR = 0.09/1.09/2.09/4.1 ms at 3T), see Fig. 2. Thus the<br />
UTILE MR- sequence enables the generation of MR-based<br />
four-class µ-maps without anatomical priors, yielding results<br />
more similar to CT-based ones than with three-class<br />
segmentation only.<br />
Translational Studies<br />
The group translational studies focuses on the late preclinical<br />
imaging and early translational research for monitoring<br />
of tumor angiogenesis, predominantly in skin, breast,<br />
kidney and liver cancer. In this regard, novel imaging techniques<br />
are being developed and evaluated in preclinical animal<br />
models. The group members are radiologists, biologists<br />
and chemists. The main focus is on functional and molecular<br />
ultrasound imaging using in-house prepared non-specific<br />
as well as targeted ultrasound contrast agents. Additionally,<br />
small animal imaging is being performed using MRI, optical<br />
imaging and PET. To verify in vivo experiments, imaging data<br />
is supplemented with immunohistochemical and other<br />
biological methods.<br />
Breast Cancer <strong>Imaging</strong>: Clinically translatable ultrasound<br />
contrast agents are tested for their potential application on<br />
humans. These contrast agents are well suited for characterizing<br />
and distinguishing breast cancer models with different<br />
angiogenesis and aggressiveness [19] . Further, the<br />
molecular information alone is better suited to discriminate<br />
differently aggressive tumor models compared to functional<br />
information alone. We now focus on examining breast<br />
cancer models during tumor growth and treatment using<br />
molecular and functional ultrasound.<br />
[17] Salomon et al, IEEE TMI 30: 804 (<strong>2011</strong>)<br />
[18] Berker et al, J Nucl Med (in press)<br />
[19] Bzyl et al, Eur Radiol 21: 1988 (<strong>2011</strong>)<br />
[20] Rix et al, Eur J Radiol (in press)<br />
<strong>2011</strong><br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
Liver <strong>Imaging</strong>: In cooperation with<br />
the group of Prof. Trautwein, transgenic<br />
mice which spontaneously develop<br />
liver fibrosis and hepatocellular<br />
carcinoma are being examined using<br />
ultrasound and MRI. The aim of these<br />
studies is to investigate the potential<br />
role of targeted ultrasound contrast<br />
agents for assessment of liver dysplasia<br />
compared to the gold standard<br />
MRI.<br />
Kidney <strong>Imaging</strong>: In cooperation with Prof. Dr. Koesters,<br />
transgenic mice which spontaneously develop renal cell<br />
cancer are being examined using ultrasound and CT. The<br />
aim of these studies is to investigate the potential role of<br />
novel ultrasound contrast agents for the characteritzation<br />
of renal cell cancer.<br />
Development of<br />
Novel <strong>Imaging</strong><br />
Probes and Techniques:<br />
For ultrasoundimaging,<br />
2D and 3D<br />
Doppler and<br />
B-mode based imaging<br />
approaches<br />
have been established<br />
[20] . Novel<br />
tumor specific<br />
contrast agents<br />
which are being<br />
synthesized,<br />
characterized and<br />
tested in vitro and<br />
in vivo.<br />
Acknowledgements<br />
This work was supported by<br />
• European Commission (FP7)<br />
• German Research Foundation (DFG)<br />
• German Federal Ministry of Education and Research<br />
(BMBF)<br />
• HighTech.NRW<br />
• START<br />
• Bracco<br />
Awards<br />
Fig. 9: 3D-Reconstruction of a tumor,<br />
used to facilitate functional and molecular<br />
ultrasound imaging.<br />
• Dennis Doleschel, Jabaduraj Jayapaul, Dr. Zhe Liu:<br />
WMIC Travel Grant<br />
• Felix Gremse: Preis für Wissenstransfer der<br />
Medizinischen Gesellschaft Aachen<br />
• Dr. Twan Lammers: DGBMT-Klee prize for<br />
Biomedical Engineering (2nd place)<br />
• Dr. Twan Lammers: International Journal of<br />
Nanomedicine Early Career Award<br />
<strong>Experimental</strong> <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
39
<strong>Experimental</strong> <strong>Molecular</strong><br />
<strong>Imaging</strong><br />
40<br />
Helmholtz-Institute for Biomedical Engineering<br />
<strong>RWTH</strong> Aachen University<br />
Most relevant Publications:<br />
[1.] Berker Y, Franke J, Salomon A, Palmowski M, Donker H, Temur Y,<br />
Mottaghy F, Kuhl C, Izquierdo D, Fayad Z, Kiessling F, Schulz V. MRbased<br />
attenuation correction for hybrid PET/MRI systems: A fourclass<br />
tissue segmentation technique using a combined ultrashort echo<br />
time (UTE)/Dixon MR sequence. J Nucl Med (in press)<br />
[2.] Bzyl J, Lederle W, Rix A, Grouls C, Tardy I, Pochon S, Siepmann M,<br />
Penzkofer T, Schneider M, Kiessling F, Palmowski M. <strong>Molecular</strong> and<br />
functional ultrasound imaging in differently aggressive breast cancer<br />
xenografts using two novel ultrasound contrast agents (BR55 and<br />
BR38). Eur Radiol <strong>2011</strong>;21:1988-1995<br />
[3.] Crielaard B, Yousefi A, Schillemans J, Vermehren C, Buyens K, Braekmans<br />
K, Lammers T, Storm G. An in vitro assay based on surface plasmon<br />
resonance to predict the in vivo circulation kinetics of liposomes.<br />
J Control Release <strong>2011</strong>;156:307-314<br />
[4.] Doleschel D, Mundigl O, Wessner A, Gremse F, Bachmann J, Rodriguez<br />
A, Klingmüller U, Jarsch M, Kiessling F, Lederle W. Targeted<br />
near-infrared imaging of the erythropoietin receptor in human lung<br />
cancer xenografts. J Nucl Med <strong>2011</strong> (in press)<br />
[5.] Fokong S., Siepmann M., Liu Z., Schmitz G., Kiessling F., Gätjens J. Advanced<br />
characterization and refinement of poly n-butyl cyanoacrylate<br />
(PBCA) microbubbles for ultrasound imaging. Ultrasound Med Biol<br />
<strong>2011</strong>;37:1622-1634<br />
[6.] Gremse F, Grouls C, Palmowski M, Vries A, Gruell H, Das M, Mühlenbruch<br />
G, Akhtar S, Schober A, Kiessling F. Virtual Elastic Sphere<br />
Processing Enables Reproducible Quantification of Vessel Stenosis in<br />
CT and MR Angiographies. Radiology <strong>2011</strong>;260:709-717<br />
[7.] Huis In ‘t Veld R, Storm G, Hennink W, Kiessling F, Lammers T. Macromolecular<br />
nanotheranostics for multimodal anticancer therapy. Nanoscale<br />
<strong>2011</strong>;4:4022-4034<br />
[8.] Jayapaul J, Hodenius M, Arns S, Lederle W, Lammers T, Comba P,<br />
Kiessling F, Gaetjens J. FMN-coated fluorescent iron oxide nanoparticles<br />
for RCP-mediated targeting and labeling of metabolically active<br />
cancer and endothelial cells. Biomaterials <strong>2011</strong>;32:5863-5871<br />
[9.] Kiessling F, Gaetjens J, Palmowski M. Application of <strong>Molecular</strong><br />
Ultrasound for <strong>Imaging</strong> Integrin Expression. Theranostics<br />
<strong>2011</strong>;1:127-134<br />
Team<br />
<strong>2011</strong><br />
[10.] Kiessling I, Bzyl J, Kiessling F. <strong>Molecular</strong> ultrasound imaging and its<br />
potential for paediatric radiology. Pediatr Radiol <strong>2011</strong>;41:176-84<br />
[11.] Lammers T, Aime S, Hennink W, Storm G, Kiessling F. Theranostic<br />
Nanomedicines. Acc Chem Res <strong>2011</strong>;44:1029-1038<br />
[12.] Lammers T, Kiessling F, Hennink W, Storm G. Drug targeting to<br />
tumors: Principles, pitfalls and (pre-)clinical progress. J Control<br />
Release (in press)<br />
[13.] Lederle W, Depner S, Schnur S, Obermueller E, Catone N, Just<br />
A, Fusenig NE, Mueller MM. IL-6 promotes malignant growth of<br />
skin SCCs by regulating a network of autocrine and paracrine cytokines.<br />
Int J Cancer <strong>2011</strong>;128:2803-2814.<br />
[14.] Liehn E, Tuchscheerer N, Kanzler I, Drechsler M, Fraehmos L,<br />
Schuh A, Koenen R, Zandler S, Soehnlein O, Hristov M, Grigorescu<br />
G, Urs A, Leabu M, Bucur I, Merx M, Zernecke A, Ehling J,<br />
Gremse F, Lammers T, Kiessling F, Bernhagen J, Schober A, Weber<br />
C. Double-edged role of the CXCL12-CXCR4 axis in experimental<br />
myocardial infarction. J Am Coll Cardiol <strong>2011</strong>;58:2415-2423<br />
[15.] Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F,<br />
Gätjens L Iron oxide nanoparticle-containing microbubble composites<br />
as contrast agents for MR and ultrasound dual-modality<br />
imaging. Biomaterials <strong>2011</strong>;32:6155-6163<br />
[16.] Rix A, Lederle W, Siepmann M, Fokong S, Behrendt FF, Bzyl J,<br />
Grouls C, Kiessling F, Palmowski M. Evaluation of high frequency<br />
ultrasound methods and contrast agents for characterising tumor<br />
response to anti-angiogenic treatment. Eur J Radiol <strong>2011</strong> (in<br />
press)<br />
[17.] Salomon A, Goedicke A, Schweizer B, Aach T, Schulz V. Attenuation<br />
maps for PET/MR uing using simultaneous reconstruction. IEEE<br />
Transaction on Medical <strong>Imaging</strong>. <strong>2011</strong>;30:804-813<br />
[18.] Truhn D, Kiessling F, Schulz V. Optimised RF Shielding Techniques for<br />
Simultaneous PET/MR. Med Phys <strong>2011</strong>;38:3995-4000<br />
[19.] Wiessler M, Hennrich U, Pipkorn R, Waldeck W, Cao L, Peter J,<br />
Ehemann V, Semmler W, Lammers T, Braun K. Theranostic cRGD-<br />
BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-<br />
<strong>Imaging</strong> and Therapy. Theranostics <strong>2011</strong>;1:381-394<br />
[20.] Xiao L, Li J, Brougham D, Fox E, Feliu N, Bushmelev A, Schmidt A,<br />
Mertens N, Kiessling F, Fadeel B, Mathur S. Water-Soluble Superparamagnetic<br />
Magnetite Nanoparticles with Biocompatible Coating<br />
for Enhanced Magnetic Resonance <strong>Imaging</strong> (MRI). ACS Nano<br />
<strong>2011</strong>;5:6315-6324