Vessel imaging with viable tumor analysis for quantification of tumor angiogenesis.
Imaging of tumor microvasculature has become an important tool for studying angiogenesis and monitoring antiangiogenic therapies. Ultrasmall paramagnetic iron oxide contrast agents for indirect imaging of vasculature offer a method for quantitative measurements of vascular biomarkers such as vessel size index, blood volume, and vessel density. Here, this technique is validated with direct comparisons to ex vivo micro-CT angiography and histologic vessel measurements, showing significant correlations between in vivo vascular MRI measurements and ex vivo structural vessel measurements. The sensitivity of the MRI vascular parameters is also demonstrated, in combination with a multispectral analysis technique for segmenting tumor tissue to restrict the analysis to viable tumor tissue and exclude regions of necrosis. It is shown that this viable tumor segmentation increases sensitivity for detection of significant effects on blood volume and vessel density by two antiangiogenic therapeutics (anti-VEGF and anti-neuropilin-1) on an HM7 colorectal tumor model. Anti-VEGF reduced blood volume by 36 +/- 3% (P < 0.0001) and vessel density by 52 +/- 3% (P < 0.0001) at 48 h posttreatment; the effects of anti-neuropilin-1 were roughly half as strong with a reduction in blood volume of 18 +/- 6% (P < 0.05) and a reduction in vessel density of 33 +/- 5% (P < 0.05) at 48 h posttreatment.
Department of Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, California 94080-4990, USA. ungersma.sharon@gene.com
Sharon E
SE
Ungersma
Glenn
G
Pacheco
Calvin
C
Ho
Sharon Fong
SF
Yee
Jed
J
Ross
Nicholas
N
van Bruggen
Franklin V
FV
Peale
Sarajane
S
Ross
Richard A D
RA
Carano
D000792:Angiography; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents