IN-VIVO IMAGING OF EXTRACTION FRACTION OF LOW-MOLECULAR-WEIGHT MR CONTRAST AGENTS AND PERFUSION RATE IN RODENT TUMORS

Tissue uptake of a fully extractable MR detectable tracer, deuterated water (D2O), was compared with that of a less extractable contrast age nt, Gadolinium-DTPA-dimeglumine (Gd-DTPA), in rodent tumor and muscle tissue, This dual tracer method allowed calculation of relative (to mu scle) tissue perfusion and extraction fraction of Gd-DTPA in each imag e pixel in vivo. Solutions of Gd-DTPA and D2O were injected intravenou sly into Fisher female rats (n = 9) with R3230 mammary adenocarcinomas implanted in the hind limb, Perfusion rate was approximately two time s greater (P < 0.005 by paired t test) in tumor than in muscle, Gd-DTP A extraction fraction at the interface between tumor and muscle was 2. 0 times the extraction fraction in normal muscle (P < 0.005 by paired t test), Extraction fraction at the tumor center was 1.6 times the ext raction fraction in muscle (P < 0.01 by paired t test), High extractio n fraction of Gd-DTPA correlated with high capillary permeability dete rmined from Evans Blue staining, Low molecular weight Gd-DTPA derivati ves are widely used in clinical practice, and their extraction fractio ns are crucial determinants of image contrast during the first few pas ses of the contrast agent bolus, Therefore spatially resolved measurem ents of contrast agent extraction fractions obtained in vivo have sign ificant clinical utility, The data demonstrate that extraction of low molecular weight tracers is sensitive to increased permeability in tum or vasculature and that this increased permeability can be imaged.