Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model.
OBJECTIVE
To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model.


METHODS
CC531 tumors were induced in WAG/Rij rats. DCE-MRI was performed before and 5 days after 5 x 5 Gy of RT and parametric maps generated of the endothelial transfer constant (K(trans)) and the fractional interstitial space (Ve) according to the Tofts model. Tissue pO2 mapping was performed in each tumor core and rim before and after RT. Microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and pimonidazole hypoxia staining were compared with a control group of tumor-bearing rats.


RESULTS
Mean K(trans) and v(e) were significantly reduced after RT in all tumor regions. Mean pO2 was 6.8 mm Hg before RT vs. 7.7 mm Hg after RT (p < 0.001) in the tumor rim and 3.5 mm Hg before RT vs. 4.4 mm Hg after RT (p < 0.001) in the tumor core. Mean MVD in the tumor rim was 10.4 in the RT treated group vs. 16.9 in the control group (p = 0.061). VEGF expression was significantly higher in RT-treated rats. After RT, no correlation was found between DCE-MRI parameters and histologic parameters. A correlation was seen after RT between pO2 and K(trans) (r = -0.57, p = 0.08) and between pO2 and v(e) (r = -0.65, p = 0.04).


CONCLUSIONS
Dynamic contrast-enhanced-MRI with P792 allows quantification of microvascular changes in this colorectal model. RT significantly reduces neovascular leakage and enhances tissue oxygenation and VEGF expression. After RT, DCE-MRI parameters are related to tumor pO2, but not to MVD or VEGF expression.
Ceelen
Wim
W
Department of Surgery, Ghent University Hospital, Ghent, Belgium. Wim.ceelen@ugent.be
Smeets
Peter
P
Backes
Walter
W
Van Damme
Nancy
N
Boterberg
Tom
T
Demetter
Pieter
P
Bouckenooghe
Isabel
I
De Visschere
Marieke
M
Peeters
Marc
M
Pattyn
Piet
P
D000818:Animals; D002199:Capillary Permeability / Q000528:radiation effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000532:radiotherapy*; D003287:Contrast Media / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008833:Microcirculation; D023421:Models, Animal; D009593:Nitroimidazoles; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D010100:Oxygen / Q000032:analysis; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; D042461:Vascular Endothelial Growth Factor A; C033815:pimonidazole; C435266:contrast agent P792; D010100:Oxygen