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-[(18)F]fluorobenzoyl)insulin ((18)F-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue (19)F-4a effectively competed with (125)I-insulin for the insulin receptor (IC50 = 10.6 nM) comparable to that for insulin (IC50 = 7.4 nM). (18)F-4b was also more stable than (125)I-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.