MEASUREMENT OF TRANSFERRIN RECEPTOR KINETICS IN THE BABOON LIVER USING DYNAMIC POSITRON EMISSION TOMOGRAPHY IMAGING AND [F-18] HOLO-TRANSFERRIN

We have evaluated the use of [F-18]holo-transferrin ([F-18]Tf) and pos itron emission tomography (PET) to measure in vivo Tf receptor express ion and recycling using the baboon liver as a model. [F-18]Tf was intr avenously injected in three baboons and dynamic PET was performed over the region containing liver and spleen. In two of the three baboons, [F-18]albumin ([F-18]Alb), labeled with the same technique, was admini stered 3 hours later. Time activity curves (TACs) were obtained from l iver and spleen for both tracers. TACs for [F-18]Tf over the liver wer e fit to a pharmacokinetic model including vascular radioactivity and an extravascular tissue compartment corresponding to transferrin uptak e and release. [F-18]Alb data provided an independent estimate of plas ma volume. Kinetic analysis showed the presence of a tissue compartmen t for [F-18]Tf that rapidly reaches equilibrium (half time 7-10 minute s). In this organ, the measured rates for Tf turnover obtained with qu antitative PET are similar to previously published data using cell cul ture systems. A model for [F-18]Tf in the spleen was not statistically improved by adding a tissue compartment. These data and the pharmacok inetic modeling provide in vivo evidence of a high flux equilibrium bi nding compartment in the liver, consistent with Tf internalization and recycling.