MRI measurements of vessel calibre in tumour xenografts: Comparison with vascular corrosion casting

作者:Burrell Jake S; Bradley Robert S; Walker Samuel Simon; Jamin Yann; Baker Lauren C J; Boult Jessica K R; Withers Philip J; Halliday Jane; Waterton John C; Robinson Simon P*
来源:Microvascular Research, 2012, 84(3): 323-329.
DOI:10.1016/j.mvr.2012.08.001

摘要

Vessel size index (R-v, mu m) has been proposed as a quantitative magnetic resonance imaging (MRI) derived imaging biomarker in oncology, for the non-invasive assessment of tumour blood vessel architecture and vascular targeted therapies. Appropriate pre-clinical evaluation of R-v in animal tumour models will improve the interpretation and guide the introduction of the biomarker into clinical studies. The objective of this study was to compare R-v measured in vivo with vessel size measurements from high-resolution X-ray computed tomography (mu CT) of vascular corrosion casts measured post mortem from the same tumours, with and without vascular targeted therapy. MRI measurements were first acquired from subcutaneous SW1222 colorectal xenografts in mice following treatment with 0 (n=6), 30 (n=6) or 200 mg/kg (n=3) of the vascular disrupting agent ZD6126. The mice were then immediately infused with a low viscosity resin and, following polymerisation and maceration of surrounding tissues, the resulting tumour vascular casts were dissected and subsequently imaged using an optimised mu CT imaging approach. Vessel diameters were not measurable by mu CT in the 200 mg/kg group as the high dose of ZD6126 precluded delivery of the resin to the tumour vascular bed. The mean R-v for the three treatment groups was 24, 23 and 23.5 mu m respectively; the corresponding mu CT measurements from corrosion casts from the 0 and 30 mg/kg cohorts were 25 and 28 mu m. The strong association between the in vivo MRI and post mortem mu CT values supports the use of R-v as an imaging biomarker in clinical trials of investigational vascular targeted therapies.

  • 出版日期2012-11