Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas.
The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF-alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K(PS) and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.
Department of Radiology, Erasmus MC-University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, The Netherlands. a.huurman@erasmusmc.nl
A
A
Preda
P A
PA
Wielopolski
T L M
TL
Ten Hagen
M
M
van Vliet
J F
JF
Veenland
G
G
Ambagtsheer
S T
ST
van Tiel
M W
MW
Vogel
A M M
AM
Eggermont
G P
GP
Krestin
C F
CF
van Dijke
D000418:Albumins; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D003287:Contrast Media; D005121:Extremities / Q000098:blood supply; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods*; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D011379:Prognosis; D051381:Rats; D011914:Rats, Inbred BN; D012513:Sarcoma, Experimental / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D000418:Albumins; D003287:Contrast Media; D046911:Macromolecular Substances; D014409:Tumor Necrosis Factor-alpha; C058946:albumin-(gadolinium-DTPA); D019786:Gadolinium DTPA; D008558:Melphalan