Toggle Main Menu Toggle Search

Open Access padlockePrints

Evaluation of the anti-vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI

Lookup NU author(s): Dr Ross Maxwell

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

The anti-vascular effects of the tubulin binding agent, disodium combretastatin A-4 3-O-phosphate (CA-4-P), have been investigated in the rat P22 carcinosarcoma by measurements of radiolabelled iodoantipyrine uptake and dynamic contrast-enhanced MRI. The iodoantipyrine estimates of absolute tumour blood flow showed a reduction from 0.35 to 0.04 ml g-1 min-1 6 h after 10 mg kg-1 CA-4-P and to <0.01 ml g-1 min-1 after 100 mg kg-1. Tumour blood flow recovered to control values 24 h after 10 mg kg-1 CA-4-P, but there was no recovery by 24 h after the higher dose. Dynamic contrast-enhanced MR images were obtained at 4.7 T, following injection of 0.1 mmol kg-1 Gd-DTPA and analysed assuming a model arterial input function. A parameter, Ktrans, which is related to blood flow rate and permeability of the tumour vasculature to Gd-DTPA, was calculated from the uptake data. Ktrans showed a reduction from 0.34 to 0.11 min-1 6 h after 10 mg kg-1 CA-4-P and to 0.07 min-1 after 100 mg kg-1. Although the magnitude of changes in Ktrans was smaller than that in tumour blood flow, the time course and dose-dependency patterns were very similar. The apparent extravascular extracellular volume fraction, e, showed a four-fold reduction 6 h after 100 mg kg-1 CA-4-P, possibly associated with vascular shutdown within large regions of the tumour. These results suggest that Ktrans values for Gd-DTPA uptake into tumours could be a useful non-invasive indicator of blood flow changes induced by anti-vascular agents such as combretastatin.


Publication metadata

Author(s): Maxwell RJ, Prise VE, Vojnovic B, Rustin GJ, Lodge MA, Tozer GM, Wilson J

Publication type: Article

Publication status: Published

Journal: NMR in Biomedicine

Year: 2002

Volume: 15

Issue: 2

Pages: 89-98

ISSN (print): 0952-3480

ISSN (electronic): 1099-1492

Publisher: John Wiley & Sons Ltd.

URL: http://dx.doi.org/10.1002/nbm.754

DOI: 10.1002/nbm.754

Notes: RJM led study. Implementaion of non-invasive magnetic resonance techniques in animals for maximal compatability with invasive animal studies and with magnetic resonance measurements in patients during early phase clinical trials.


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share