COMPARATIVE KINETICS OF MICROVASCULAR INULIN AND TC-99M-LABELED DIETHYLENETRIAMINEPENTA-ACETIC ACID EXCHANGE

1. After simultaneous intravenous injection as a mixture, Tc-99m-label led diethylenetriaminepentaacetic acid (Tc-99m-DTPA; molecular mass 49 2 Dal and inulin (similar to 6000 Dal gave arterial plasma clearance c urves 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 (norm alized to the ratio in arterial plasma at 30 s) was 0.6, significantly less than unity, within 2 min after intravenous injection, but increa sed to reach unity by 60 min, The minimun concentration ratio of Tc-99 m-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 fo r inulin (similar to 0.2), For both solutes, the net extraction fracti on decreased with time, becoming negative at about 25 min after inject ion, Thereafter, the net extraction fractions remained negative, betwe en -0.05 and -0.1, and not significantly different between the two sol utes, 4, Tc-99m-DTPA time-activity curves recorded over the limbs with scintillation probes were biphasic, with an initial phase correspondi ng closely in time with the first exponential of the arterial Tc-99m-D TPA plasma clearance curve, The second phase corresponded in time to t he intermediate exponential of the arterial Tc-99m-DTPA plasma clearan ce curve, 5, The time course of net (99m)Tcm-DTPA extraction fraction across the forearm vascular bed was hi-exponential, with phases corres ponding in time with the two phases of the limb uptake curves, 6, Deco nvolution analysis of the limb time-activity curves, using the arteria l 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 na ture of the equilibrium of Tc-99m-DTPA between vascular and interstiti al compartments suggests the presence of two separate functional volum es within the interstitial space, Although Tc-99m-DTPA and inulin clea rly diffuse at different rates across the endothelium, as would be exp ected from their disparate sizes, the similarity in the time courses o f 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 vol umes, however, are not significantly different between the two solutes .