title: Structure--activity relationship and preclinical evaluation of carbon-11-labeled ammonium salts as PET--myocardial perfusion imaging agents.
abstract: BACKGROUND
  Due to the limited availability of suitable positron emission tomography (PET) tracers, the majority of myocardial perfusion imaging (MPI) scans is performed using SPECT rather than PET.
  
  
  OBJECTIVE
  The aim of this study is to design and synthesize carbon-11-labeled ammonium salt derivatives and explore their structure–activity relationship (SAR) and their potential as PET–MPI agents.
  
  
  RESULTS
  Three carbon-11-labeled ammonium salts were developed. SAR of the labeled compounds were explored vis-à-vis the effects of charge density and lipophilicity on the distribution kinetics in mice. These studies pointed at [11C]4 as the lead compound. Comparative microPET/CT scans in healthy rats, using both [11C]4 and [13 N]–NH3, substantiated the potential of [11C]4 ([11C]-DMDPA). A proof of concept for the potential of radiolabeled ammonium salts as MPI agents has been demonstrated in a newly developed swine model of permanent partial coronary artery occlusion.
  
  
  CONCLUSIONS
  SAR studies of 11C-labeled ammonium salts suggest that both lipophilicity and charge density affect the performance of these compounds as MPI probes. In a swine model, the labeled lead successfully visualized the defect regions in the myocardium. The data presented call for the development of fluorine-18 analogues, to increase clinical impact.
authors.affiliation: Cyclotron/Radiochemistry Unit/Nuclear Medicine Department, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Ilovich
authors.forename: Galith
authors.initials: G
authors.lastname: Abourbeh
authors.forename: Moshe
authors.initials: M
authors.lastname: Bocher
authors.forename: Nanette
authors.initials: N
authors.lastname: Freedman
authors.forename: Hana
authors.initials: H
authors.lastname: Billauer
authors.forename: Sharon
authors.initials: S
authors.lastname: Dotan
authors.forename: Haim D
authors.initials: HD
authors.lastname: Danenberg
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000000981:diagnostic imaging; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging; D055414:Myocardial Perfusion Imaging; D049268:Positron-Emission Tomography; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D051381:Rats; D012492:Salts / Q000737:chemistry; D013329:Structure-Activity Relationship; D034421:Sus scrofa; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D000644:Quaternary Ammonium Compounds; D012492:Salts