title: 4-[18F]Fluoro-m-hydroxyphenethylguanidine: a radiopharmaceutical for quantifying regional cardiac sympathetic nerve density with positron emission tomography.
abstract: 4-[(18)F]Fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG, [(18)F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [(18)F]1 was developed in which the intermediate 4-[(18)F]fluoro-m-tyramine ([(18)F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [(18)F]fluorination. In PET imaging studies in rhesus macaque monkeys, [(18)F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [(18)F]1 kinetics provided net uptake rate constants Ki (mL/min/g wet), and Patlak graphical analysis of [(18)F]1 kinetics provided Patlak slopes Kp (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [(18)F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET.
authors: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School , 2276 Medical Sciences I Building, Ann Arbor, Michigan 48109, United States.
authors: Keun Sam
authors: KS
authors: Jang
authors: Yong-Woon
authors: YW
authors: Jung
authors: Guie
authors: G
authors: Gu
authors: Robert A
authors: RA
authors: Koeppe
authors: Phillip S
authors: PS
authors: Sherman
authors: Carole A
authors: CA
authors: Quesada
authors: David M
authors: DM
authors: Raffel
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D005260:Female; D005462:Fluorine Radioisotopes; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000882:Haplorhini; D006321:Heart / Q000294:innervation*; D006801:Humans; D008297:Male; D010627:Phenethylamines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging*
chemical_list: C583191:4-fluoro-3-hydroxyphenethylguanidine; D005462:Fluorine Radioisotopes; D006146:Guanidines; D010627:Phenethylamines; D019275:Radiopharmaceuticals
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