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 18F into peptides and showed that 18F-labeled insulin (18F-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 18F-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 18F-insulin (approximately 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 18F was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, approximately 1 nmol) with the 18F-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 18F was predominantly in bile and urine. 18F-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney.
Eastman
R C
RC
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Carson
R E
RE
Jacobson
K A
KA
Shai
Y
Y
Channing
M A
MA
Dunn
B B
BB
Bacher
J D
JD
Baas
E
E
Jones
E
E
Kirk
K L
KL
D000818:Animals; D005462:Fluorine Radioisotopes; D007328:Insulin / Q000378:metabolism* / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008253:Macaca mulatta; D011972:Receptor, Insulin / Q000032:analysis* / Q000378:metabolism; D013997:Time Factors; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D007328:Insulin; D011972:Receptor, Insulin