NONINVASIVE MEASURES OF RADIOLABELED DEXTRAN TRANSPORT IN IN-SITU RABBIT LUNG

Dextrans are nontoxic and can be obtained in a wide variety of molecul ar weights. The purpose of this study was to label 6-kDa and 40-kDa de xtrans with gamma- (Tc-99m) and positron- (F-18) emitting radioisotope s and monitor their transport across the pulmonary microvascular barri er. Methods: External scan measurements for radiolabeled uncharged dex trans, albumin and red blood cells were obtained ill eight blood-perfu sed in situ rabbit lung preparations. After 3 hr of external scanning, the lungs were removed for postmortem and extravascular distribution volume calculations. Extravascular distribution volumes were obtained in six additional rabbits following 4 hr of dextran perfusion to compa re the effect of time. The normalized slope index (NSI), a measure of transvascular transport rate, was calculated for each diffusible trace r. Results: The mean NSI for albumin (0.001676 +/- 0.000537 min(-1)) w as significantly lower than NSI for the 40-kDa dextran (0.002303 +/- 0 .0005426 min(-1)) as well as the 6-kDa dextran (0.004312 +/- 0.001134 min(-1)). The difference between the 6-kDa and the 40-kDa dextrans was also significant. After 4 hr of equilibration, distribution volumes w ere not significantly different than those obtained at 3 hr. Conclusio n: Dextrans can be radiolabeled with gamma and positron emitters and s mall dextrans traverse the lung microvascular barrier more rapidly tha n albumin. Our results suggest that the use of small dextrans rather t han albumin can reduce scan times in clinical applications and minimiz e motion artifact associated with the noninvasive gamma detection meth od.