INVIVO IMAGING OF INSULIN-RECEPTORS IN MONKEYS USING F-18 LABELED INSULIN AND POSITRON EMISSION TOMOGRAPHY

We previously described a prosthetic group methodology for incorporating F-18 into peptides and showed that F-18-labeled insulin (F-18-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 F-18-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 F-18-insulin (approximately 0.1 nmol, SA 4-11 Ci/mu-mol). 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 F-18 was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, approximately 1 nmol) with the F-18-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 F-18 was predominantly in bile and urine. F-18-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney.