In vivo microscopic evaluation of the microvascular behavior of FITC-labeled macromolecular MR contrast agents in the hamster skinfold chamber

RATIONALE AND OBJECTIVES. The extravasation properties of two macromolecula r MR imaging contrast media (CM) in relation to structural differences of t he terminal vascular bed were investigated to determine whether differentia tion between normal (physiological) and tumor (pathological) tissue can be achieved by means of extravasation characteristics. METHODS. Gd-DTPA-polylysine (50 kD, CM1) and Gd-DOTA cascade polymer (Gadom er 17; 20 kD, CM2) were labeled with fluorescein isothiocyanate (FITC) to e nable in vivo fluorescence microscopy of the microcirculation. After implan tation of a dorsal skinfold chamber and 7 days (range, 6-8) after induction of an amelanotic melanoma (A-Mel-3), 14 male hamsters weighing 85 g (range , 70-95 g) received 200 mu mol/kg of CM1 by intravenous injection into the jugular vein, CM2 was similarly investigated after an interval of 24 hours. Fluorescence microscopy was performed in areas of subcutaneous tissue, str iated muscle, and tumor tissue. Microscopic images Were registered by a cha rge-coupled-device video camera and transferred to a video system, Distribu tion intensities of CM were evaluated on a digitally based measurement syst em,A control investigation was performed with FITC-dextran (150 kD), RESULTS. Gd-DTPA-polylysine showed no extravasation into physiological tiss ue for the first 10 minutes after injection. After this period, however, th e first signs of leakage became apparent. Gd-DOTA cascade polymer was extra vasated after 5 minutes into the tumor-free tissue, In tumor capillaries, G d-DTPA-polylysine could be detected in the extravasal space as well as in p hysiological tissue after 15 minutes, After injection of Gd-DOTA cascade po lymer, direct leakage from tumor capillaries was observed, with a contrast maximum between tumor and surrounding tissue occurring 3 to 5 minutes after CM injection, Good delineation of tumor vascularization from striated musc le and subcutaneous tissue was achieved. CONCLUSIONS. The CM studied showed different microvascular permeation prope rties. Faster leakage of Gd-DOTA cascade polymer was observed in areas with neoplastic tumor vessels, whereas extravasation in physiological tissue wa s detected after a period of 5 minutes. Gd-DTPA-polylysine demonstrated non specific leakage at later time points.