1. Contrast Media Mol Imaging. 2010 Nov-Dec;5(6):323-32.

Surrogate MR markers of response to chemo- or radiotherapy in association with
co-treatments: a retrospective analysis of multi-modal studies.

Jordan BF, Gallez B.

Laboratory of Biomedical Magnetic Resonance, Louvain Drug Research Institute,
Université Catholique de Louvain, Avenue Mounier 73, B-1200 Brussels, Belgium.

The study of magnetic resonance (MR) markers over the past decade has provided
evidence that the tumor microenvironnement and hemodynamics play a major role in 
determining tumor response to therapy. The aim of the present work is to predict 
and monitor the efficacy of co-treatments to radio- and chemotherapy by
noninvasive MR imaging. Ten different co-treatments were involved in this
retrospective analysis of our previously published data, including NO-mediated
co-treatments (insulin and isosorbide dinitrate), anti-inflammatory drugs
(hydrocortisone, NS-398), anti-angiogenic agents (thalidomide, SU5416 and
ZD6474), a vasoactive agent (xanthinol nicotinate), botulinum toxin and carbogen 
breathing. Dynamic contrast enhanced (DCE) MRI, intrinsic susceptibility-weighted
(BOLD) MRI and electronic paramagnetic resonance (EPR) oximetry all reflect tumor
microenvironment hemodynamic variables that are known to influence tumor
response. Eight MR-derived parameters (markers) were tested for their ability to 
predict therapeutic outcome (factor of increase in regrowth delay) in
experimental tumor models (TLT and FSaII) after radiation therapy and/or
chemotherapy with cyclophosphamide, namely tumor pO₂ and O₂ consumption rate
(using EPR oximetry); tumor blood flow and permeability, i.e. V(p), K(trans),
K(ep) and percentage of perfused vessels (using DCE-MRI); and BOLD signal
intensity and R₂* (using functional MRI). This multi-modal comparison of
co-treatment efficacy points out the limitations of each MR marker and identifies
in vivo pO₂ as a relevant endpoint for radiation therapy. DCE parameters (V(p)
and K(ep)) were identified as a relevant endpoints for cyclophosphamide
chemotherapy in our tumor models. This study helps qualify relevant imaging
endpoints in the preclinical setting of cancer therapy.


PMID: 20648644 [PubMed - in process]