A molecular imaging paradigm to rapidly profile response to angiogenesis-directed therapy in small animals.
OBJECTIVE
The development of novel angiogenesis-directed therapeutics is hampered by the lack of non-invasive imaging metrics capable of assessing treatment response. We report the development and validation of a novel molecular imaging paradigm to rapidly assess response to angiogenesis-directed therapeutics in preclinical animal models.


METHODS
A monoclonal antibody-based optical imaging probe targeting vascular endothelial growth factor receptor-2 (VEGFR2) expression was synthesized and evaluated in vitro and in vivo via multispectral fluorescence imaging.


RESULTS
The optical imaging agent demonstrated specificity for the target receptor in cultured endothelial cells and in vivo. The agent exhibited significant accumulation within 4T1 xenograft tumors. Mice bearing 4T1 xenografts and treated with sunitinib exhibited both tumor growth arrest and decreased accumulation of NIR800-alphaVEGFR2ab compared to untreated cohorts (p = 0.0021).


CONCLUSIONS
Molecular imaging of VEGFR2 expression is a promising non-invasive biomarker for assessing angiogenesis and evaluating the efficacy of angiogenesis-directed therapies.
Virostko
John
J
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Xie
Jingping
J
Hallahan
Dennis E
DE
Arteaga
Carlos L
CL
Gore
John C
JC
Manning
H Charles
HC
D000818:Animals; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods*; D042783:Endothelial Cells / Q000473:pathology; D051379:Mice; D015336:Molecular Probe Techniques; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*; D023041:Xenograft Model Antitumor Assays
D040301:Vascular Endothelial Growth Factor Receptor-2