Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.
We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.
Laboratoire de Recherche en Imagerie, LRI-U494, Faculte Necker, Paris, France.
C
C
Pradel
N
N
Siauve
G
G
Bruneteau
O
O
Clement
C
C
de Bazelaire
F
F
Frouin
S R
SR
Wedge
J L
JL
Tessier
P H
PH
Robert
G
G
Frija
C A
CA
Cuenod
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D045744:Cell Line, Tumor; D003287:Contrast Media; D018810:Magnetic Resonance Angiography; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D011799:Quinazolines; D014230:Triazoles; D042461:Vascular Endothelial Growth Factor A; C405268:ZD 4190