Increase in tumour permeability following TGF-beta type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI.

Abstract:

BACKGROUND:To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent. METHODS:To apply transforming growth factor (TGF)-beta type I receptor (TbetaR-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium (Gd)-DTPA and for its liposomal formulation to evaluate changes in tumour microvasculature following A-83-01. Tumour vascular parameters from DCE-MRI were compared with histological assessment and apparent diffusion coefficient of water in tumour generated by diffusion-weighted MRI. RESULTS:Contrary to evaluations reported for anti-angiogenic agents, A-83-01 treatment increased the initial area under the Gd concentration-time curve (IAUGC60), volume transfer constant (K(trans)) and fractional plasma volume (v(p)) significantly within 24 h, that was positively related to alpha-smooth muscle actin-positive pericyte coverage and tumour cell proliferation, and was correlated inversely with the apparent diffusion coefficient. The vascular function of the tumour improved by A-83-01 treatment was well assessed on post-liposomal Gd-DTPA-enhanced MR images, which predicted delivery of a liposomal drug to the tumour. CONCLUSION:These findings suggest that DCE-MRI and, in particular, K(trans) and v(p) quantitation, provide important additional information about tumour vasculature by A-83-01 treatment.

journal_name

Br J Cancer

authors

Minowa T,Kawano K,Kuribayashi H,Shiraishi K,Sugino T,Hattori Y,Yokoyama M,Maitani Y

doi

10.1038/sj.bjc.6605367

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

1884-90

issue

11

eissn

0007-0920

issn

1532-1827

pii

6605367

journal_volume

101

pub_type

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