title: Synthesis and bioevaluation of [(18)F]4-fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG): a novel radiotracer for quantitative PET studies of cardiac sympathetic innervation.
abstract: A new cardiac sympathetic nerve imaging agent, [(18)F]4-fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [(18)F]4-fluoro-m-tyramine ([(18)F]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [(18)F]4F-MHPG. Initial bioevaluations of [(18)F]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [(11)C]4F-MHPG. The neuronal uptake rate of [(18)F]4F-MHPG into the isolated rat heart was 0.68ml/min/g wet and its retention time in sympathetic neurons was very long (T1/2 >13h). A PET imaging study in a nonhuman primate with [(18)F]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80-90min after injection of 5-to-1. These initial kinetic and imaging studies of [(18)F]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents.
authors: Division of Nuclear Medicine, Department of Radiology, 2276 Medical Science I Building, 1301 Catherine Street, University of Michigan Medical School, Ann Arbor, MI 48109, United States.
authors: Keun Sam
authors: KS
authors: Jang
authors: Yong-Woon
authors: YW
authors: Jung
authors: Phillip S
authors: PS
authors: Sherman
authors: Carole A
authors: CA
authors: Quesada
authors: Guie
authors: G
authors: Gu
authors: David M
authors: DM
authors: Raffel
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006207:Half-Life; D006321:Heart / Q000000981:diagnostic imaging; D008253:Macaca mulatta; D008734:Methoxyhydroxyphenylglycol / Q000737:chemistry* / Q000493:pharmacokinetics; D009206:Myocardium / Q000378:metabolism; D010627:Phenethylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D014018:Tissue Distribution
chemical_list: C583191:4-fluoro-3-hydroxyphenethylguanidine; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D006146:Guanidines; D010627:Phenethylamines; D008734:Methoxyhydroxyphenylglycol