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

Vessel size index (R_v, μm) 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 (μCT) 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 200mg/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 μCT imaging approach. Vessel diameters were not measurable by μCT in the 200mg/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 23.5μm respectively; the corresponding μCT measurements from corrosion casts from the 0 and 30mg/kg cohorts were 25 and 28μm. The strong association between the in vivo MRI and post mortem μCT values supports the use of R_v as an imaging biomarker in clinical trials of investigational vascular targeted therapies.