Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas

• Published in: Magma (New York, N.Y.) Vol. 17; no. 3-6; pp. 296 - 302
• Main Authors: Preda, A, Wielopolski, P A, Ten Hagen, T L M, van Vliet, M, Veenland, J F, Ambagtsheer, G, van Tiel, S T, Vogel, M W, Eggermont, A M M, Krestin, G P, van Dijke, C F
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-12-2004
• Subjects: Albumins; Animals; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Chemotherapy, Cancer, Regional Perfusion - methods; Contrast Media; Extremities - blood supply; Gadolinium DTPA; Image Enhancement - methods; Macromolecular Substances; Magnetic Resonance Imaging - methods; Male; Melphalan - administration & dosage; Prognosis; Rats; Rats, Inbred BN; Sarcoma; Sarcoma, Experimental - diagnosis; Sarcoma, Experimental - drug therapy; Treatment Outcome; Tumor Necrosis Factor-alpha - administration & dosage
• ISSN: 0968-5243; 1352-8661; 1352-8661
• DOI: 10.1007/s10334-004-0050-z

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.