Is 3D MR molecular imaging of neovasculature prognostic of tumor response to antiangiogenic therapy?

Abstract

αvβ3—targeted fumagillin nanoparticles suppress the neovasculature and inhibit tumor growth in Vx2 tumors. The objective of this study was to use MR molecular imaging and 3D neovascular mapping tools to quantify antiangiogenic and tumor growth responses to integrin‐targeted fumagillin nanoparticles in a xenograft tumor model.Methods:Nude mice implanted with MDA435 cells received ανβ3‐targeted fumagillin nanoparticles, α5β1‐targeted fumagillin nanoparticles, or saline on days 7, 11, 15, and 19 post implantation. On day 22, tumor volume and neovascularity were assessed using integrin‐targeted MR nanoparticles.Results:Neovascularity was sparser in the xenograft model than observed in Vx2 rabbits. α5β1–fumagillin‐nanoparticles decreased (p<0.05) angiogenesis relative to control (1.3±0.3%) to an almost negligible level (0.5±0.3 %) while αvβ3–fumagillin‐nanoparticles did not decrease (p>0.05) angiogenesis (1.0±0.3%, Fig). Neither treatment regimen affected tumor volume.Conclusion:Tumors expressing low levels of neovascularity have poor tumor growth response to antiangiogenic treatment. Nascent cancers responsive to antiangiogenic therapy may be differentiated with noninvasive high‐resolution MR molecular imaging, which may be clinically relevant in establishing personalized therapy regimens. Support NIH/NCI CA 119342