Comparative kinetics of microvascular inulin and Tc-99m-labelled diethylenetriaminepenta-acetic acid exchange

1. After simultaneous intravenous injection as a mixture, Tc-99m-labelled diethylenetriaminepentaacetic acid (Tc-99m-DTPA; molecular mass 492 Dal and inulin (similar to 6000 Dal gave arterial plasma clearance curves consisting of three exponentials, the time courses of which were not significantly different between the two solutes, 2, The ratio of Tc-99m-DTPA to inulin concentration in antecubital venous plasma (normalized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increased to reach unity by 60 min, The minimun concentration ratio of Tc-99m-DTPA to inulin in arterial plasma was 0.75 at 4 min, also rising to just above unity at 60 min, 3. The extraction fraction from plasma to interstitial space was higher for Tc-99m-DTPA (similar to 0.5) than for inulin (similar to 0.2), For both solutes, the net extraction fraction decreased with time, becoming negative at about 25 min after injection, Thereafter, the net extraction fractions remained negative, between -0.05 and -0.1, and not significantly different between the two solutes, 4, Tc-99m-DTPA time-activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase corresponding closely in time with the first exponential of the arterial Tc-99m-DTPA plasma clearance curve, The second phase corresponded in time to the intermediate exponential of the arterial Tc-99m-DTPA plasma clearance curve, 5, The time course of net (99m)Tcm-DTPA extraction fraction across the forearm vascular bed was hi-exponential, with phases corresponding in time with the two phases of the limb uptake curves, 6, Deconvolution analysis of the limb time-activity curves, using the arterial time-concentration curve as the input function, gave bi-exponential Tc-99m- DTPA impulse response curves in which the time courses of the exponentials corresponded with the first and intermediate exponentials of the arterial Tc-99m-DTPA clearance curve, 7, The bi-exponential nature of the equilibrium of Tc-99m-DTPA between vascular and interstitial compartments suggests the presence of two separate functional volumes within the interstitial space, Although Tc-99m-DTPA and inulin clearly diffuse at different rates across the endothelium, as would be expected from their disparate sizes, the similarity in the time courses of their initial exponentials and simultaneous equalization of transfer rates (i.e. when net extraction fraction was zero) is consistent with the hypothesis that inulin moves initially into a smaller functional interstitial fluid volume than Tc-99m-DTPA. The total distribution volumes, however, are not significantly different between the two solutes.