A substituted (18)F insulin derivative has been synthesized for study of insulin receptors in vivo by positron emission tomography (PET). Using a novel prosthetic group methodology 18F insulin can be prepared in 4 hours with a specific activity of 4-12 curies/micromole at the time of administration. In vivo studies have been performed in 7 Rhesus monkeys to determine whether the F insulin binds to insulin receptors in vivo. Under basal conditions there is rapid, specific, and reversible uptake of the label by liver and kidney at tracer concentrations in the low picomolar range. Binding to liver is irreversible 5 minutes after injection, while s significant component of kidney uptake can be displaced, suggesting different kinetics for insulin uptake in these tissues. Excretion of the radioactivity is predominantly in bile and urine.
