Pathological animal models in the experimental evaluation of tumour microvasculature with magnetic resonance imaging

The purpose of this study was to evaluate the applications of magnetic resonance imaging (MRI), and in particular, dynamic contrast-enhanced MRI (DCE-MRI), in the assessment of tumour microvasculature by means of animal tumour models evaluated before and after antiangiogenic treatment.

Forty-two MRI exams were performed with intravascular contrast media in 21 rats: tumours were induced by subcutaneous injection of colon carcinoma cells in 7 rats and mammary adenocarcinoma cells in 14 rats. Perfusion and permeability parameters of the implanted tumours were evaluated by using two contrast media (B22956/1 and Gd-DTPA37-albumin) to establish response to treatment with two different antiangiogenic drugs (tamoxifen and SU6668). These parameters were correlated with histology to obtain a radiological-histological map of tumour microvasculature.

DCE-MRI revealed greater enhancement in the peripheral area than in the central area in all the examined animal models. In the mammary carcinoma experiment, vascular permeability measured by means of B22956/1 in the animals treated with the antiangiogenic drug (0.0043317+/-0.0040418 ml/min(-1)/ml(-1)) was significantly less than in untreated animals (0.0090460+/-0.0043680 ml/min(-1)/ml(-1)), whereas no significant difference was observed with Gd-DTPA-albumin (13.14+/-13.94 ml/min(-1)/ml(-1) in treated animals and 18.07+/-11.92 ml/min(-1)/ml(-1) in untreated animals). In the colon carcinoma experiment, mean permeability and perfusion decreased by 51% (from 5.2+/-1.1 to 2.5+/-0.8 ml/100 ml) and 59% (from 0.00165+/-5.1 to 0.0067+/-4.8 ml/min(-1)/ml(-1) of tissue), respectively, in all animals after antiangiogenic drug administration.

DCE-MRI permits a noninvasive evaluation of tumour microcirculation and in particular of its dynamic characteristics and vascularity before and after antiangiogenic treatment.