[F-18]labeiing of 1,2-diacylglycerols

Article abstract of DOI:10.1002/1099-1344(200008)43:9<943::AID-JLCR379>3.0.CO;2-V

We have developed two kinds of [¹⁸F]labeled 1,2-diacylglycerols (1,2-DAGs) such as 1-(ω-[¹⁸F]fluoroacyl)-2-acylglycerols (1*,2-[¹⁸F]FDAGs) and 2-(ω[¹⁸F]fluoroacyl)-1-acylglycerols (1,2*-[¹⁸F]FDAGs) for imaging receptor-mediated phosphatidyl-inositol (PI) turnover responses by positron emission tomography (PET). The 1*,2-[¹⁸F]FDAGs were synthesized by the reaction of 2-monoacyl glycerols with ω-[¹⁸F]fluoroacyl chlorides (method A) and 1-(16-[¹⁸F]fluoro palmitoyl)-2-palmitoylglycerol (1*,2-[¹⁸F]FDAG(C16,C16)) and 1-(8-[¹⁸F]fluoro octanoyl)-2-palmitoylglycerol (1*,2-[¹⁸F]FDAG(C8,C16)) were synthesized using method A. However, during the synthesis of 1,2*-[¹⁸F]FDAGs, we adopted the hydrogenolysis to remove a benzyl group from 3-O-benzyl-2-(ω-[¹⁸F]fluoroacyl)-1-acylglycerol, which was synthesized by the nucleophilic exchange reaction of 3-O-benzyl-2-(ω-bromoacyl)-1-acylglycerol with [¹⁸F]F^- (method B) and 2-(16-[¹⁸F]fluoropalmitoyl)-1-palmitoylglycerol (1,2*-[¹⁸F]FDAG(C16,C16)) and 2-(8-[¹⁸F]fluorooctanoyl)-1-palmitoylglycerol (1,2*-[¹⁸F]FDAG(C16,C8)) were produced using method B. The purified 1*,2-[¹⁸F]FDAGs were obtained in radiochemical yields of 8-35% (based on [¹⁸F]F^-) with radiochemical purities of > 97% and the purified 1,2*-[¹⁸F]FDAGs were in radiochemical yields of 5-15% with radiochemical purities of > 95%. The total synthesis time from the start of the reactive [¹⁸F]F^- production, including HPLC purification, was 100-135 min (method A) and 115-175 min (method B), respectively. It has already been used for more than 100 preparations of 1*,2-[¹⁸F]FDAG(C16,C16), 1*,2-[¹⁸F]FDAG (C8,C16), and 1,2*-[¹⁸F]FDAG(C16,C16), 1,2*-[¹⁸F]FDAG(C16,C8) for animal studies.