The determination of mass of metabolites with tracers

Application of tracers in vivo for the determination of replacement and mass of bloodborne compounds at steady state is discussed. Theory and methods to determine mass with tracers (total amount of compound-tracee-within the body) for compartmental and noncompartmental systems are presented, and their limitations examined. Methods to derive mass from the specific activity curves after bolus injection or infusion of tracer are described using graphic procedures or by equations using the parameters of exponential curves. The relationship between assumed models and the interpretation of tracer data is examined. The determination of both replacement (appearance, which equals utilization at steady state) and mass of most compounds present in both extracellular and intracellular fluids (such as lactate and amino acids) requires the application of the A-V mode for tracer administration and sampling of blood. Recycling of carbon affects the determination of mass with 14C. Estimates of true mass are provided with tritium-labeled compounds, even when tritium loss is by exchange with protons or through futile cycling. Estimates of the amount (body mass) of lactate, alanine, glutamate, and proline obtained with tritium-labeled compounds are presented. Most of these masses are intracellular. The concentration of lactate in tissues equals or is greater, and that of amino acids much greater than that in plasma. Hence, the so-called "distribution space" for these compounds, calculated conventionally by dividing mass by plasma concentration, would appear to be equal to or greater than the body water of lactate, and several liters per kilogram for amino acids.