PET is a powerful technique for measuring the regional metabolism of radiolabelled tracers in
vivo, but the question remains how to convert the clearance of an analogue tracer measured by PET to the
clearance of its mother substance, e.g., for [18F]fluoro-2-deoxy-D-glucose (18F-FDG) and glucose. The ratio
between the extraction fraction of the tracer (E*) and that of the mother substance (E), as measured by
arteriovenous concentrations across the organ, is often used as a proportionality factor for converting the
PET-determined clearance of tracer to the clearance of the mother substance. However, this approach is
founded in compartmental modelling which assumes a well-mixed concentration in the vascular compartment
equal to the inlet (arterial) blood concentration. For the in vivo situation with perfused capillaries (for
the liver, sinusoids), the removal of substrate from the blood by the cells creates concentration gradients in
the capillary/sinusoid. We recently derived and validated that the lumped constant (Λ) equals ln(1–E*)/ln(1–
E), being a correct in vivo proportionality factor in capillary beds for the removal of tracer and mother
substance in the cells. This relationship is independent of the concentration of the mother substance, whereas
E*/E may vary with the concentration of the mother substance.
Keywords: Tracer kinetics; Lumped constant; Bi-substrate enzyme kinetics; Sinusoidal microcirculation;
Intrinsic clearance; Positron emission tomography; 18F-FDG; 18F-FDGal.