Dynamic contrast-enhanced magnetic resonance imaging and oxygenation measurements were performed 5 days before and 5 days after the completion of RT. Magnetic resonance imaging The principle of DCE-MRI consists of serial measurements of signal intensity changes in both tumour Navitoclax Bcl-xL tissue and a feeding artery after bolus injection of a paramagnetic CA. Depending on the physical properties of the CA and the leakiness of the microvessel wall, a fraction of the CA will reach the interstitial space of the tumour, where an increase in signal intensity over time will be observed. After translation of signal intensity changes to CA concentration values, pharmacokinetic modelling allows calculation of physiological properties such as microvessel permeability and tumour blood volume.

Dynamic contrast studies were performed with P792, a new monogadolinated rapid clearance MRI blood-pool CA, which is cleared by renal elimination. The molecular weight of the compound is 6.47kDa, but the mean diameter of P792 is 50.5 ? and the T1 relaxivity of this agent is 29mM?1s?1 at 60MHz (Port et al, 2001a). The apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA (gadoterate meglumine, Dotarem) and as a result of this high molecular volume, P792 is characterised by a limited diffusion across the normal endothelium and therefore ideally suited to study hyperpermeable neoplastic vessels (Port et al, 2001b). Experimentally, P792 has been used to study permeability effects of anti-angiogenesis therapy in a prostate cancer model (Pradel et al, 2003).

We have previously demonstrated that P792 selectively enhances tumour tissue in this colorectal cancer model (Ceelen et al, 2006). T1-weighted DCE-MRI was performed on a Siemens Magnetom Symphony? 1.5T scanner (Siemens AG, Erlangen, Germany). Animals were sedated with 0.2�C0.4ml of medetomidine (Domitor?, Novartis Animal Health, Basel, Switzerland). Imaging comprised a single axial slice that was positioned through both lower limbs and the centre of the tumour. Before the contrast series, T1 zero time maps were constructed from two spin echo sequences with different repetition times (TR 1000 and 318ms, respectively). Details of this sequence were as follows: slice thickness 3mm, field of view (FOV) 140 �� 88, matrix size 256 �� 160, echo time (TE) 20ms, and flip angle 90��.

Dynamic Dacomitinib imaging was performed with a 4-antenna wrist coil (diameter 10cm) using an inversion recovery TurboFLASH sequence. Details of the pulse sequence were as follows: temporal resolution 1.1s (i.e. TR 1100ms), FOV 140 �� 88, matrix size 256 �� 160, slice thickness 5mm, TE 4.08ms, inversion time 560ms, and flip angle 12��. A bolus of 0.3�C0.4ml of P792 was manually injected as fast as possible (approximately 1mls?1) through a central venous line after the fourth scan.