| Molecular & Cellular Probes |
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Tuesday 21 April 2009 |
| Room 316BC |
10:30-12:30 |
Moderators: |
Michael T. McMahon and Willem M. Mulder |
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10:30 |
222. |
The Development of an MR Agent
for Imaging of Malignant Micro-Calcification in
Breast Cancer |
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Kumar R. Bhushan1,
Elena Vinogradov2, Ananth J.
Madhuranthakam3, Atshushi Takahashi4,
John V. Frangioni1,2, Robert E. Lenkinski2
1Medicine, Beth Israel Deaconess Medical
Center, Boston, MA, USA; 2Radiology, Beth
Israel Deaconess Medical Center, Boston, MA, USA;
3Applied Science Laboratory, GE
Healthcare, Boston, MA, USA; 4Applied
Science Laboratory, GE Healthcare, Menlo Park, CA,
USA |
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We have developed
lanthanide-chelated bisphosphonate derivatives that
are suitable MRI agents for imaging hydroxyapatite.
An ultra-short echo time (UTE) sequence was used to
image these agents in the environment of
micro-calcification. We found that these compounds
possess very high relaxivity in the adsorbed state.
The combination of UTE and the newly developed MR
agents demonstrate the successful high specificity
and high sensitivity detection of calcified
substances in vitro and in vivo. This study
provides a foundation for the design and development
of methods for high sensitivity MR detection of
micro-calcifications within breast tumors. |
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10:42 |
223. |
Fluorine-19 MR Molecular Imaging of Angiogenesis on
Vx-2 Tumors in Rabbits Using α ν β 3-Targeted
Nanoparticles |
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Jochen Keupp1,
Shelton D. Caruthers2,3, Jürgen Rahmer1,
Todd A. Williams3, Samuel A. Wickline3,
Gregory M. Lanza3
1Philips Research Europe, Hamburg, Germany;
2Philips Healthcare, Andover, MA, USA;
3Washington University, St. Louis, MO,
USA |
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Anti-angiogenic therapy
in combination with established chemotherapy or
radiation therapy has entered clinical practice for
lung, colon and breast cancer. However,
effectiveness of anti-angiogenic pre-treatment is
substantially varying among patients. Given the high
cost and severe side effects, there is a strong
clinical need for enhanced patient stratification,
which could be based on MRI of angiogenesis using
targeted imaging agents. ανβ3-integrin targeted
nanoparticle (NP) emulsions, labeled with
R1-enhancing Gd-chelates, were previously shown to
allow three-dimensional MR mapping of tumor
angiogenesis in small animals. These studies were
based on δR1 mapping from two image sets taken
before and after NP injection. The present study
shows, that the perfluorocarbon (PFC) core of the
same targeted NP can be used as a 19F MR
label to map angiogenesis around Vx-2 tumors (adenocarcinoma)
in rabbits. With simultaneous 19F and
1H MR, diagnostic imaging is only
required at a single time point post-injection
injection and may offer the ability of direct
absolute quantification. |
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10:54 |
224. |
In Vivo Molecular MRI
of Atherosclerotic Plaque Progression in Mice Using
a Novel Elastin-Binding Contrast Agent |
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Marcus R. Makowski1,
Ulrike Blume1, Andrea J. Wiethoff1,
Christian Jansen1, Joel Lazewatsky2,
Simon Robinson2, Rene M. Botnar3
1King’s College London BHF Centre of Research
Excellence, Imaging Sciences Division, London, UK;
2Lantheus Medical Imaging, USA; 3King’s
College London BHF Centre of Research Excellence,
Imaging Sciences Division, UK |
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The extracellular matrix
(ECM) plays a pivotal role in the pathogenesis of
atherosclerosis and ECM remodeling. Elastin is an
essential component of the ECM of the arterial
vessel wall. Male ApoE -/- mice have been shown to
reproducibly develop progressive atherosclerotic
plaques in the innominate artery over a short period
on a high fat diet (HFD). With the advent of a novel
elastin binding contrast agent (BMS -753951) imaging
of ECM formation in atherosclerosis has become
feasible. In this study, we demonstrate the
successful non-invasive assessment of alterations in
atherosclerotic plaque size in an ApoE mouse model
using serial MRI together with a novel elastin
specific contrast agent. Molecular alterations, with
regard to elastin formation in atherosclerosis can
be differentiated using BMS-753951. |
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11:06 |
225. |
MR Imaging of an Arachidonic
Acid-Induced Mouse Model of Thrombosis Using an
Activated Platelets-Targeted Paramagnetic Contrast
Agent |
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Ahmed Klink1,2,
Eric Lancelot3, Sébastien Ballet3,
Walter Gonzalez3, Christelle Medina3,
Claire Corot3, Jean-Etienne Fabre4,
Willem J.M Mulder1, Ziad Mallat2,
Zahi A. Fayad1
1Translational and Molecular Imaging
Institute, Mount Sinai School Of Medicine, New York,
NY, USA; 2INSERM U689, Paris, France;
3Research Division, Guerbet, France;
4Atherothrombosis Laboratory, Institut de
Génétique et de Biologie Moléculaire et Cellulaire,
Strasbourg, France |
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P975 is a paramagnetic
MRI based contrast agent with specificity for
activated platelets via a peptide that binds to the
glycoprotein GPIIb/IIIa. This agent was used in an
arachidonic acid-induced mouse model of thrombosis
to visualize thrombi formation and monitor
thrombogenic activity. |
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11:18 |
226. |
in Vivo CEST Imaging
Using Eu(III)-Water Molecule Exchange System |
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Tomoyasu Mani1,2,
Osamu Togao1, Todd C. Soesbe1,
Masaya Takahashi1, Allan Dean Sherry1,2
1Advanced Imaging Research Center, University
of Texas Southwestern Medical Center at Dallas,
Dallas, TX, USA; 2Department of
Chemistry, University of Texas at Dallas,
Richardson, TX, USA |
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Chemical exchange
saturation transfer (CEST) imaging has attracted
considerable attention. Ln(III)-based exogenous CEST
agents (PARACEST) can be used to enhance the
sensitivity of CEST imaging. As part of a program to
develop more effective agents, a newly designed
Eu(III)-DOTA-tetraamide complex was applied in
vivo. The CEST effect from this agent were
somewhat smaller when the agent was dissolved in
blood plasma at body temperatures (35-39 C) compared
to when it was dissolved in pure water. No
differences in CEST were observed at lower
temperatures (20-27 C). CEST contrast in liver and
kidney of mouse (20%) were successfully observed
using low presaturation pulse (7µT) to avoid
competitive inherent MT effects. |
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11:30 |
227. |
Magnetization Transfer
Detection of GFP: A New MRI Gene Reporter |
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Carlos J.
Perez-Torres1, Cynthia A. Massaad2,
Faridis Serrano2, Robia G. Pautler1,2
1Translational Biology and Molecular Medicine
Program, Baylor College of Medicine, Houston, TX,
USA; 2Department of Molecular Physiology
and Biophysics, Baylor College of Medicine, Houston,
TX, USA |
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To visualize gene
expression via any imaging modality, a reporter
system needs to be instituted that causes sufficient
contrast between the tissues where the gene is
expressed compared to other tissues where the gene
is not expressed. Green Fluorescent Protein (GFP) is
a widely used molecular and gene expression marker.
We report a technique to detect GFP by using
Magnetic Resonance Imaging (MRI) through
Magnetization Transfer Contrast (MTC). GFP was
detected with MTC MRI both in vitro and in vivo.
This system provides a flexible, non-invasive in
vivo molecular imaging system that has the
advantage of combining readily available materials. |
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11:42 |
228. |
Chimeric Ferritin as a
Reporter for MRI |
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Bistra Iordanova1, Clinton S. Robison1,
Eric T. Ahrens1,2
1Department of Biological Sciences, Carnegie
Mellon University, Pittsburgh, PA, USA; 2Pittsburgh
NMR Center for Biomedical Research, Carnegie Mellon
Univeristy, Pittsburgh, PA, USA |
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Several recent molecular
MRI techniques utilize the iron storage protein
ferritin as a probeless reporter. One of the
practical limitations of ferritin as a reporter for
MRI is that it is a relatively weak contrast agent,
especially at lower magnetic field strengths. To
enhance MRI sensitivity, we fixed its heavy and
light subunit stoichiometry by engineering a fusion
single-chain ferritin. In this study we show that
the new ferritin chimera loads significantly more
iron and exhibits higher transverse relaxation rates
than wild type ferritin both in human cells and in
mouse brain. |
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11:54 |
229. |
In Vivo MR and PET
Imaging of a Highly Sensitive Polymeric PARACEST
Contrast Agent |
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Todd C. Soesbe1,
Yunkou Wu2, Guiyang Hao3,
Xiankai Sun1, A. Dean Sherry1,2
1Advanced Imaging Research Center, The
University of Texas Southwestern Medical Center at
Dallas, Dallas, TX, USA; 2Department of
Chemistry, The University of Texas at Dallas,
Dallas, TX, USA; 3Department of
Radiology, The University of Texas Southwestern
Medical Center at Dallas, Dallas, TX, USA |
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Chemical exchange
saturation transfer (CEST) agents create contrast in
MR images by exchanging their saturated lanthanide
bound protons with those of bulk water. These agents
have great potential to further extend the
functional and molecular imaging capabilities of MR.
Polymeric paramagnetic CEST (PARACEST) agents have
recently been prepared by our group. The polymeric
agents increase the CEST effect by creating a higher
concentration of lanthanide ions at the target site.
These agents offer an order on magnitude improvement
in sensitivity which greatly reduces in vivo
dose levels. The improved sensitivity of the
polymeric agents also helps overcome the
magnetization transfer (MT) effect due to endogenous
macromolecules in tissue, which can mask the CEST
effect. We present the first in vivo images
of a polymeric Eu3+ PARACEST agent using a simple
fast spin echo pulse sequence. We also show that
this agent could be used for simultaneous PET/MR
imaging by labeling the polymer with Cu-64. |
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12:06 |
230. |
Rational Design of a High
Relaxivity MR Probe |
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Luca Frullano1,
Peter Caravan1
1Radiology, Massachusetts General Hospital,
Charlestown, MA, USA |
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The synthesis and
characterization of a new Gd-based contrast agent is
described. A dual strategy of increasing
inner-sphere and second-sphere hydration was used to
design an agent with more than 150% higher
relaxivity than other low molecular weight contrast
agents. Relaxivity is unaffected by the presence of
coordinating anions such as phosphate or citrate and
the high relaxivity is maintained over a broad field
range (0.5 – 9.4T). This complex also contains a
pendant carboxylate for linkage of this contrast
agent to a putative targeting moiety such as a
peptide. |
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12:18 |
231. |
Well-Defined, Multifunctional Nanostructures of a
Paramagnetic Lipid and a Lipopeptide for Macrophage
Imaging |
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Honorius M.H.F.
Sanders1,2, Esad Vucic3, Nico
A.J.M. Sommerdijk2, Enzo Terreno4,
Francesca Arena4, Silvio Aime4,
Klaas Nicolay1, Margaritta Dathe5,
Zahi A. Fayad3, Willem J.M. Mulder3
1Biomedical NMR, Department of Biomedical
Engineering, Eindhoven University of Technology,
Eindhoven, Brabant, Netherlands; 2Soft
Matter Cryo-TEM Research Unit, Eindhoven University
of Technology, Eindhoven, Brabant, Netherlands;
3Translational and Molecular Imaging Institute
and Imaging Science Laboratories, Mount Sinai School
of Medicine, New York, USA; 4Department
of Chemistry IFM and Molecular Imaging Center,
University of Torino, Torino, Italy; 5Leibniz
Institute of Molecular Pharmacology, Berlin, Germany |
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In the field of targeted
molecular imaging and therapy the pharmacokinetic
profile as well as the tissue penetration potential
of nanoparticulate formulations is of paramount
importance. Hence, there is a great demand for
nanostructures of which the final morphology and
size can be judiciously controlled.
By controlling the ratio
of two amphiphilic molecules, the paramagnetic lipid
Gd-DTPA-DSA and P2fA2, a fluorscein labeled
apolipoprotein E derived lipopeptide, we created a
variety of well-defined multifunctional and nano-sized
structures. NMRD-profiling disclosed excellent and
tunable MRI properties, while in vitro
experiments with macrophage cells demonstrated
efficient uptake. |
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