In Vivo Imaging of Insulin Receptors in Monkeys Using 18F-Labeled Insulin and Positron Emission Tomography

We previously described a prosthetic group methodology for incorporating 18 F into peptides and showed that 18 F-labeled insulin ( 18 F-insulin) binds to insulin receptors on human cells (IM-9 lymphoblastoid cells) with affinity equal to that of native insulin (1). We now report studies using 18 F-insulin with positron emission tomography to study binding to insulin receptors in vivo. Positron emission tomography scans were performed in six rhesus monkeys injected with 0.3–1.4 mCi of 18 F-insulin (∼ 0.1 nmol, SA 4–11 Ci/mumol). Integrity of the tracer in blood, determined by immunoprecipitation, was 94% of control for the first 5 min and decreased to 31% by 30 min. Specific, saturable uptake of 18 F was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, ∼ 1 nmol) with the 18 F-insulin reduced liver and increased kidney uptake of the labeled insulin. Liver radioactivity was decreased by administration of unlabeled insulin at 3 min, but not 5 min, after administration of the tracer, while some kidney radioactivity could be displaced 5 min after injection. Clearance of 18 F was predominantly in bile and urine. 18 F-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney.