| Preclinical & Human Studies of Tumor Therapy Response |
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Wednesday 22 April 2009 |
| Room 315 |
10:30-12:30 |
Moderators: |
Kristine Glunde and N. R. Jagannathan |
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10:30 |
409. |
Edema Control by Anti-VEGF
Therapy Prolongs Survival Despite Persistent Tumor
Growth in Mice |
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Christian T. Farrar1,
Walid Kamoun2, Carsten D. Ley2,
Young R. Kim1, Guangping Dai1,
Bruce R. Rosen1, Rakesh K. Jain2,
A. Gregory Sorensen1
1Athinoula A. Martinos Center for Biomedical
Imaging, Department of Radiology, Massachusetts
General Hospital, Charlestown, MA, USA; 2Edwin
L. Steele Laboratory, Department of Radiation
Oncology, Massachusetts General Hospital, Boston,
MA, USA |
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Recent clinical trials
of anti-vascular endothelial growth factor (VEGF)
agents for glioblastoma showed promising
progression-free and overall survival rates.
However, it is unclear whether this is due to
anti-tumor or anti-edema effects of these agents.
Thus the mechanisms leading to improved survival in
patients remain unclear. Our goal was to determine
whether alleviation of edema by anti-VEGF agents
alone, without affecting tumor growth, could
increase survival in mice. Here we examine in detail
the impact of cediranib treatment on tumor growth,
tumor blood volume, vessel caliber, edema, and
permeability in a U87 mouse brain tumor model. In
addition, we validate the MRI biomarkers of tumor
angiogenesis with histology, optical microscopy, and
wet-dry weight measurement methods. |
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10:42 |
410. |
Noninvasive Therapeutic
Evaluation on Rodent Liver Tumor Treated with
Vascular Disrupting Agent: Multiparametric Magnetic
Resonance Imaging in Correlation with
Microangiography and Histology |
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Huaijun Wang1,
Junjie Li1, Feng Chen1,
Yicheng Ni1
1Catholic University of Leuven, Leuven, East
Flanders, Belgium |
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This study aimed to
document tumoricidal events after a vascular
targeting agent ZD6126 in rodent liver tumors with
clinical MRI in correlation with postmortem
microangiography and histopathology.
Rhabdomyosarcomas in rat liver were treated with i.v.
injection of ZD6126. Therapeutic outcomes were
evaluated morphologically and functionally with 1.5T
MRI. Diffusion-weighted imaging and dynamic
contrast-enhanced MRI successfully monitored
vascular shutdown by ZD6126 at 1h after treatment,
prior to the advent of morphological change of tumor
size at 48h, which were verified with
microangiography and histopathology. Clinical MRI
allowed monitoring of ZD6126-related vascular
shutdown, necrosis, and neovascularization of liver
tumors in rats. |
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10:54 |
411. |
Vessel Size Index MRI for
Evaluating the Effects of Multiple Anti-Angiogenic
Therapies in Sequence |
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Sharon E. Ungersma1,
Glenn Pacheco2, Anil Bagri1,
Shang-Fan Yu2, Andrew Mcgeehan2,
Sarajane Ross2, Richard A.D. Carano1
1Tumor Biology & Angiogenesis, Genentech,
South San Francisco, CA, USA; 2Translational
Oncology, Genentech, South San Francisco, CA, USA |
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In vivo imaging
of tumors treated with anti-angiogenic agents can
reveal information about therapeutic effects on
tumor vasculature. Vessel size index (VSI) MRI uses
a USPIO contrast agent to determine the blood
volume, mean vessel size, and Q (a parameter related
to vessel density) for each voxel. We used VSI MRI
to examine the effects of two potential therapies in
sequence: anti-VEGF, an antibody to vascular
endothelial growth factor, and anti-NRP1B,
an anti-angiogenic agent believed to inhibit vessel
maturation. The VSI technique detected significant
reductions in vascular parameters that indicated an
advantage to dosing with anti-NRP1B
before anti-VEGF. |
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11:06 |
412. |
Assessment of Vascular
Remodelling During Antiangiogenic Tumor Therapy
Using DCE-MRI and Vessel Size Imaging |
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Stefan Zwick1,
Ralph Strecker2, Moritz Palmowski3,
Peter Gall4, Valerij Kiselev4,
Arne Hengerer2, Wolfhard Semmler1,
Fabian Kiessling3
1Medical Physics in Radiology, German Cancer
Research Center, Heidelberg, Germany; 2HealthCare
Sector, Siemens AG, Erlangen, Germany; 3Department
of Experimental Molecular Imaging, RWTH-Aachen
University, Aachen, Germany; 4Department
of Diagnostic Radiology, University Hospital
Freiburg, Freiburg, Germany |
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To assess vascular
remodelling in tumors during antiangiogenic therapy
DCE-MRI and vessel size imaging were performed.
Tumor bearing nude mice were treated with a
multitargeted tyrosine kinase inhibitor and
investigated before and after treatment. The
decrease of A and increase of kep in treated
compared to untreated tumors clearly showed therapy
response. The mean vessel size measured by vessel
size imaging significantly increased in treated as
compared to untreated tumors. Results of both
methods are in excellent agreement with histology.
Thus, DCE-MRI and vessel size imaging were able to
assess vascular remodelling during antiangiogenic
tumor therapy. |
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11:18 |
413. |
Measurement of the Increase in
Vessel Size Induced by a Vascular Disrupting Agent
in Orthotopic Prostate Tumours Using Vessel Size
Imaging |
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Simon Walker-Samuel1,
Jessica K. Boult1, Lesley D. McPhail1,
Simon P. Robinson1
1Cancer Research UK Clinical Magnetic
Resonance Research Group, Institute of Cancer
Research, Sutton, Surrey, UK |
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In this study,
susceptibility MRI with ultra-small paramagnetic
iron oxide (USPIO) was used to estimate the vessel
size index (VSI) in orthotopic PC3 prostate tumours
following treatment with ZD6126, a vascular
disrupting agent. It was found that orthotopic
tumours exhibited larger vessels than typically
found in ectopic (subcutaneous) tumour xenograft
models (VSI = 65±25ìm), and that this significantly
increased following treatment with ZD6126
(post-treatment VSI = 122±36ìm, p<0.05). An
excellent correspondence was found with histological
measurements of vessel size. This study highlights
the potential use of VSI as a biomarker for
assessing vascular architecture and response to
vascular disrupting agents. |
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11:30 |
414. |
Can DCE MRI Predict Risk of
Treatment Failure in Early-Stage Favorable-Prognosis
Cervical Cancer Patients? |
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Nina A. Mayr1,
William T.C. Yuh2, Hualin Zhang1,
Lanchun Lu1, Joe F. Montebello1,
Steffen Sammet2, Guang Jia2,
Jeffrey M. Fowler3, Kyle Porter4,
David Jarjoura4, Jian Z. Wang1
1Radiation, The Ohio State University,
Columbus, OH, USA; 2Radiology, The Ohio
State University, Columbus, OH, USA; 3Obstetrics
& Gynecology, The Ohio State University, Columbus,
OH, USA; 4Biostatistics, The Ohio State
University, Columbus, OH, USA |
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Despite favorable
prognosis, many low risk cervical cancer patients
ultimately fail therapy. The purpose of this study
was to assess, if DCE MRI can predict poor treatment
outcome in patients with otherwise favorable
clinical prognosis judged by gold-standard clinical
criteria. DCE MRI predicts treatment failure early
in otherwise favorable-prognosis cervical cancer
patients and provides a therapeutic window to modify
the treatment strategies that can have profound
impact to the long term outcome. This predictive
ability is likely related to DCE MRI’s ability to
indentify and analyze the subregions of the
heterogeneous tumor that likely represent tumor
cells resistant to treatment. |
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11:42 |
415. |
Combining DCE-MRI and
Microbubble Ultrasound to Evaluate Response to
Sunitinib in Patients with Renal Cell Carcinoma |
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Colleen Bailey1,2,
Ross Williams2, Gord Lueck2,
Mostafa Atri3, Peter N. Burns1,2,
Greg J. Stanisz1,2, Georg A. Bjarnason4
1Medical Biophysics, University of Toronto,
Toronto, ON, Canada; 2Imaging Research,
Sunnybrook Health Sciences Centre, Toronto, ON,
Canada; 3Medical Imaging, Sunnybrook
Health Sciences Centre, Toronto, ON, Canada; 4Medical
Oncology, Sunnybrook Health Sciences Centre,
Toronto, ON, Canada |
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Patients with renal cell
carcinoma were treated with the drug Sunitinib and
examined by DCE-MRI and contrast-enhanced
ultrasound. DCE-MRI provided the volume transfer
constant, Ktrans, and the extravascular
extracellular volume fraction ve.
Disruption-replenishment provided the relative blood
volume change. Combining the information from both
imaging techniques provides a fuller picture of the
tumour response to treatment. |
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11:54 |
416. |
Potential of Choline SNR,
Tumor Volume and Diameter in the Assessment of
Response of Locally Advanced Breast Cancer Patients
Using Sequential MRSI and MRI |
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Karikanni Kalathil A.
Danishad1, Uma Sharma1, Rani
Gupta Sah1, Vurthaluru Seenu2,
Rajinder Parshad2, Naranamangalam R.
Jagannathan1
1Department of NMR and MRI Facility, All India
Institute of Medcial Sciences, New Delhi, Delhi,
India; 2Department of Sugical
Disciplines, All India Institute of Medcial
Sciences, New Delhi, Delhi, India |
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Sequential MRSI [before
therapy and after I, II and neo-adjuvant
chemotherapy (NACT)] was carried out in 30 breast
cancer patients to evaluate the potential of
signal-to-noise ratio of choline (ChoSNR), tumor
volume and diameter to predict tumor response.
Changes in these parameters revealed significant
decrease in ChoSNR after I NACT compared to
pre-therapy in responders than non-responders.
Sensitivity to detect responders using ChoSNR was
85.7% with 91% specificity while 100% sensitivity
for volume and diameter but with reduced specificity
(73% and 81.8%). When all the three parameters were
combined, 100%sensitivity, 82% specificity with
87.5% PPV and 100% NPV was achieved. |
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12:06 |
417. |
Choline Metabolites as
Biomarkers for Predicting Response to Neoadjuvant
Chemotherapy in Local Advanced Breast Cancer
Patients |
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Maria Dung Cao1,
Beathe Sitter1, Tone Frost Bathen1,
Per E. Lønning2,3, Steinar Lundgren1,4,
Ingrid Susann Gribbestad1
1Department of Circulation and Medical
Imaging, Norwegian University of Science and
Technology (NTNU), Trondheim, Norway; 2Department
of Oncology, Haukeland University Hospital, Bergen,
Norway; 3University of Bergen, Bergen,
Norway; 4Department of Oncology, St.Olavs
University Hospital, Trondheim, Norway |
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The presence and change
in the composite choline signal detected in MR
spectra has been suggested as a biomarker for breast
cancer diagnosis and treatment monitoring. The
purpose of this study was to evaluate quantitative
changes in the level and composition of the choline-containing
metabolites (tCho) prior to and after treatment with
doxorubicin monotherapy in 30 patients with breast
cancer. Our study suggests that quantitative changes
in different choline profiles may be related to
breast cancer treatment response. |
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12:18 |
418. |
Noninvasive Detection of
Carboxypeptidase G2 Activity in Vivo using
19F 3D CSI |
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Yann Jamin1,
Lynette Smyth1, Simon P. Robinson1,
Thomas R. Eykyn1, Caroline J. Springer1,
Martin O. Leach1, Geoffrey S. Payne1
1Institute of Cancer Research and Royal
Marsden NHS trust, Sutton, UK |
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Carboxypeptidase G2
(CPG2) is a bacterial enzyme used in cancer
chemotherapy to activate selectively non toxic
prodrugs into potent cytotoxics in tumors. We
demonstrate that 19F 3D CSI can be used
in combination with a surface coil to monitor
dynamically and quantitatively the CPG2-mediated
conversion of the reporter probe
3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu)
into 3,5-difluorobenzoic acid (3,5-DFBA). This
method could provide important information on the
level of CPG2 activity in patient undergoing
CPG2-based therapy. |
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