ESTRO 36 Abstract Book

S199 ESTRO 36 _______________________________________________________________________________________________

Poster Viewing : Session 8: Radiobiology

PV-0369 The potential of hyperpolarized ¹³C MRS to monitor the effect of vascular disrupting agents A. Iversen 1 , M. Busk 1 , L. Bertelsen 2 , C. Laustsen 2 , O. Munch 3 , T. Nielsen 4 , T. Wittenborn 1 , J. Bussink 5 , J. Lok 5 , H. Stødkilde-Jørgensen 2 , M. Horsman 1 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 13 C-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. Kim 1 , T. Koo 2 , B. Cho 3 , E. Choi 3 , D. Lee 3 , H. Kim 3 , D. Kim 3 , J. Park 3 1 Seoul National University School of Medicine, Radiation Oncology, Seoul, Korea Republic of 2 Seoul National University Graduate School of Medicine, Radiation Oncology, Seoul, Korea Republic of 3 Seoul 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.