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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma
Ingrid Leguerney1,2, Ludovic de Rochefort1, Marie Poirier-Quinot1
1IR4M, UMR 8081, Paris-Sud University, CNRS, Bâtiment 220, rue Ampère, 91405 Orsay Cedex, France.
Abstract:
Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R = 0.87, p = 0.0003) and AUC (R = 0.81, p = 0.0013). The percentage of vessel tissue area was significantly reduced (p < 0.01) in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.
Insights
Molecular MRI targeting αvβ3 and DCE-US detect early neoangiogenesis changes in renal cell carcinoma treated with targeted therapies. These imaging techniques show promise for monitoring treatment response and guiding clinical trials.
Area of Science:
- Oncology
- Medical Imaging
- Pharmacology
Background:
- Renal cell carcinoma (RCC) treatment response assessment is crucial.
- Neoangiogenesis plays a key role in RCC progression and treatment.
- Early detection of therapeutic effects on tumor vasculature is needed.
Purpose of the Study:
- To compare molecular magnetic resonance imaging (MRI) targeting αvβ3 integrin with dynamic contrast-enhanced ultrasound (DCE-US) and immunohistochemistry.
- To assess the early response of sunitinib, everolimus, and bevacizumab in a renal cell carcinoma model.
- To evaluate the potential of αvβ3-targeted molecular MRI for monitoring neoangiogenesis.
Main Methods:
- Subcutaneous inoculation of human A498 renal cells into nude mice.
- Treatment with phosphate-buffered saline, sunitinib, everolimus, or bevacizumab for 4 days.
- Performance of DCE-US and αvβ3-targeted molecular MRI at baseline and after 4 days of treatment.
- Comparison of perfusion index (PI), area under the curve (AUC), ΔR2*, and CD31-stained microvessel area.
Main Results:
- DCE-US showed significant decreases in PI and AUC for the bevacizumab group by day 4.
- αvβ3-targeted MRI detected significant changes in both bevacizumab and everolimus groups.
- CD31 microvessel area correlated significantly with DCE-US parameters (PI and AUC).
- Vessel tissue area was significantly reduced in sunitinib and bevacizumab groups.
Conclusions:
- Both DCE-US and αvβ3-targeted molecular MRI can detect early modifications in neoangiogenesis following targeted therapy in RCC.
- αvβ3-targeted MRI demonstrated sensitivity to changes induced by both anti-angiogenic (bevacizumab) and mTOR inhibitor (everolimus) therapies.
- The findings support further clinical development of molecular MRI for evaluating targeted therapy efficacy in RCC.
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