Dose Response of Rat GH3 prolactinomas to 5,6-dimethylxanthenone-4-acetic acid (DMXAA) Assessed by Dynamic Contrast Enhanced MRI
Kestell P, Griffiths J, Kelland L, Robinson S, McIntyre D, McPhail L, Ludwig C
University of Auckland
Tumour vasculature is an attractive therapeutic target. The dose-dependent effects of DMXAA, a vascular disrupting agent which induces selective occlusion of tumour blood vessels and necrosis, were investigated using dynamic contrast-enhanced (DCE) MRI, measurements of 5-hydroxyindoleacetic acid (5-HIAA), which is a plasma biomarker of DMXAA-induced anti-vascular activity, and tumour necrosis. DCE MRI revealed a significant reduction in Ktrans and IAUGC of rat GH3 prolactinomas 24 hours after treatment with 350mg/kg DMXAA, but there was no evidence of dose response. A significant increase in 5-HIAA, associated with DMXAA-induced increase in vascular permeability, was measured in response to 200 and 350mg/kg DMXAA.