Fluorine-18 labeled insulin: a prosthetic group methodology for incorporation of a positron emitter into peptides and proteins

In the present study we synthesize 18F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which [18F]fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. 18F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides.