Preparation and Evaluation of Fluorine-18-Labeled Insulin as a Molecular Imaging Probe for Studying Insulin Receptor Expression in Tumors

A convenient emulsion-based labeling method was used to synthesize fluorine-18-labeled insulin specifically B-1-(4-[F-18]fluorobenzoyl)insulin (F-18-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue F-19-4a effectively competed with I-125-insulin for the insulin receptor (IC50 = 10.6 nM) comparable to that for insulin (IC50 = 7.4 nM). F-18-4b) was also more stable than I-125-insulin in mouse plasma with 50% remaining intact after 30 min. A biodistribution study in normal mice showed initial uptake of the tracer in the kidneys, liver, and gall bladder but rapid clearance via the urine/bladder which was also observed in murine models bearing insulin receptor positive tumors.