title: Effect of the prosthetic group on the pharmacologic properties of 18F-labeled rhodamine B, a potential myocardial perfusion agent for positron emission tomography (PET).
abstract: We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Bartholomä
authors.forename: Vijay
authors.initials: V
authors.lastname: Gottumukkala
authors.forename: Shaohui
authors.initials: S
authors.lastname: Zhang
authors.forename: Amanda
authors.initials: A
authors.lastname: Baker
authors.forename: Patricia
authors.initials: P
authors.lastname: Dunning
authors.forename: Frederic H
authors.initials: FH
authors.lastname: Fahey
authors.forename: S Ted
authors.initials: ST
authors.lastname: Treves
authors.forename: Alan B
authors.initials: AB
authors.lastname: Packard
mesh_terms: D000818:Animals; D004952:Esters; D005462:Fluorine Radioisotopes; D006018:Glycols / Q000737:chemistry; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D051379:Mice; D055414:Myocardial Perfusion Imaging; D009206:Myocardium / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012235:Rhodamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D004952:Esters; D005462:Fluorine Radioisotopes; D006018:Glycols; D019275:Radiopharmaceuticals; D012235:Rhodamines; C029773:rhodamine B