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Is 3D MR molecular imaging of neovasculature prognostic of tumor response to antiangiogenic therapy?
Author(s) -
Caruthers Shelton D,
Schmieder Anne,
Winter Patrick,
Williams Todd A,
Allen John S,
Hu Grace,
Zhang Huiying,
Wickline Samuel,
Lanza Gregory
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.898.40
Subject(s) - fumagillin , angiogenesis , medicine , cancer research , in vivo , pathology , biology , microbiology and biotechnology
α v β 3 —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 α ν β 3 ‐targeted fumagillin nanoparticles, α 5 β 1 ‐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. α 5 β 1 –fumagillin‐nanoparticles decreased (p<0.05) angiogenesis relative to control (1.3±0.3%) to an almost negligible level (0.5±0.3 %) while α v β 3 –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