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

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• 作者：Dong Hyun Kim ; Megan Blacker ; John F. Valliant
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：May 8, 2014
• 年：2014
• 卷：57
• 期：9
• 页码：3678-3686
• 全文大小：451K
• 年卷期：v.57,no.9(May 8, 2014)
• ISSN：1520-4804

文摘

A convenient emulsion-based labeling method was used to synthesize fluorine-18-labeled insulin specifically B¹-(4-[¹⁸F]fluorobenzoyl)insulin (¹⁸F-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue ¹⁹F-4a effectively competed with ¹²⁵I-insulin for the insulin receptor (IC₅₀ = 10.6 nM) comparable to that for insulin (IC₅₀ = 7.4 nM). ¹⁸F-4b was also more stable than ¹²⁵I-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.