Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCEUS 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 DCEUS 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.