First Radiolabeling of a Ganglioside with a Positron Emitting Radionuclide: In Vivo PET Demonstrates Low Exposure of Radiofluorinated GM1 in Non-human Primate Brain.

Gangliosides are biologically important glycolipids widely distributed in vertebrate cells. An important member of the ganglioside family is the monosialylganglioside GM1, which has been suggested as a potential therapeutic for Parkinson's disease. In the current study, a late-stage radiofluorination protocol was developed, in which fluorine-18 was introduced by substitution of a terminal tosyl group in the fatty acid backbone of GM1. The radiofluorination procedure was remarkably simple and furnished the radiofluorinated ganglioside, [18F]F-GM1, in sufficient quantity and quality without protection of the glycosyl moiety. A positron emission tomography measurement in cynomolgus monkey revealed high uptake of [18F]F-GM1 in heart, bone marrow, and lungs but low (<0.4% of injected dose) distribution to the brain. Thus, choosing administration route of GM1 for therapy of central nervous system disorders poses further challenges. The present study demonstrates the importance of application of positron emission tomography microdosing studies in guiding early clinical drug development.