ESTRO 36 Abstract Book

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S199 ESTRO 36
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Poster Viewing : Session 8: Radiobiology
PV-0369 The potential of hyperpolarized ¹³C MRS to
monitor the effect of vascular disrupting agents
A. Iversen1, M. Busk1 , L. Bertelsen2, C. Laustsen2, O.
Munch3, T. Nielsen4 , T. Wittenborn1, J. Bussink5, J. Lok5,
H. Stødkilde-Jørgensen2 , M. Horsman1
1 Aarhus University Hospital, Department of Experimental
Clinical Oncology, Aarhus C, Denmark
2 Aarhus University Hospital, Institute for Clinical
Medicine- MR Research Centre, Aarhus C, Denmark
3 Aarhus University Hospital, PET Centre, Aarhus C,
Denmark
4 Aarhus University Hospital, Center of Functionally
Integrative Neuroscience, Aarhus C, Denmark
5 Radboud University Medical Center, Department of
Radiation Oncology, Nijmegen, The Netherlands
Purpose or Objective
Targeting tumor vasculature with vascular disrupting
agents (VDAs) is attractive. Since treatment effects
precedes tumor shrinkage, ways of detecting metabolic
changes to assess treatment efficacy are warranted.
Positron emission tomography (PET) using
fluorodeoxyglucose (FDG) is currently a first-choice
imaging approach for early assessment of metabolic
changes during treatment. However, hyperpolarized ¹³C
magnetic resonance spectroscopy (MRS) is more refined
since it allows dynamic measurements of the metabolism
of 13C-labeled substrates in vivo. The aim of this study is
to investigate the potential of hyperpolarized ¹³C MRS to
monitor the vascular changes induced by combretastatin-
A4-phosphate and it structural analogue OXi4503.
Material and Methods
The VDAs combretastatin-A4-phosphate (CA4P) and
OXi4503 were tested in mice bearing subcutaneous C3H
mammary carcinomas. Hyperpolarized [1-¹³C]pyruvate
was intravenously injected while hyperpolarized ¹³C MRS
was performed with a 9.4 T MRI scanner and parameters
of interest was calculated. Other, similarly treated, mice
were PET scanned using a nanoScan Mediso PET/MRI
scanner following administration of FDG. Ultimately,
metabolic imaging results were compared to direct
measures of vascular damage derived from dynamic
contrast-agent enhanced magnetic resonance imaging
(DCE-MRI) and histological analysis and to the clinical
relevant endpoint tumor regrowth delay.
Results
Treatment efficacy was confirmed by DCE-MRI, tissue and
tumor growth analysis, which revealed profound vascular
damage and associated changes in blood-flow-related
parameters, cell death and slowed tumor growth. FDG-
PET revealed early detectable changes in signal, which
may reflect true changes in glucose metabolism, impaired
FDG delivery or a mixture of both. Nonetheless, the ratio
of [1-¹³C]lactate/[1-¹³C]pyruvate area under the curve
(AUC ratio) and the lactate time-to-peak (TTP), calculated
from hyperpolarized ¹³C MRS, was unaffected by
treatment.
Fig. 1. FDG-PET as a means to visualize and quantify early
metabolic changes during VDA treatment. A: FDG-PET/MRI
images showing a PBS treated (control) and an OXi4503
treated tumor-bearing mice. Arrows indicate tumor
location. B: bar charts shows summarized data for all
treatments using SUV or reference-tissue-based
quantification of whole-tumor average or tumor sub-
volume glucose metabolism. Mean values ± SD are plotted.
P < 0.05; *, P < 0.001; **. C: scatterplot showing the close
relationship between PET-derived and Packard-derived
(ground truth) whole-tumor to whole-brain tracer ratios.
D: examples of high-resolution invasive analysis of the
intratumoral distribution of FDG retention.
Conclusion
Even though DCE-MRI and FDG-PET demonstrated
significant changes after treatment with VDAs, the
hyperpolarized ¹³C MRS AUC ratio and the lactate TTP did
not change. Further experiments including additional
tumor models and validation against established
technologies are needed to explore the usefulness of
hyperpolarized ¹³C MRS for early predicting of VDA
efficacy.
PV-0370 MicroRNA-200c radiosensitizes Human Cancer
Cells with Activated EGFR or HER2-associated Signaling
I.A. Kim1, T. Koo2, B. Cho3, E. Choi3, D. Lee3, H. Kim3, D.
Kim3, J. Park3
1Seoul National University School of Medicine, Radiation
Oncology, Seoul, Korea Republic of
2Seoul National University Graduate School of Medicine,
Radiation Oncology, Seoul, Korea Republic of
3Seoul National Univ. Bundang Hospital, Medical Science
Research Institute, Seongnam- Gyeonggi-Do, Korea
Republic of
Purpose or Objective
A member of the miRNA-200 family, miRNA-200c (miR-
200c), recently was found to have tumor-suppressive
properties by inhibiting the epithelial-mesenchymal
transition (EMT) process in several cancers . miR-200c also
interacts with various cellular signaling molecules and
regulates many important signaling pathways. In the
present study, we investigated the radiosensitizing effect
of miR-200c and the mechanism of radiosensitization in a
panel of human cancer cell lines.