title: Rat imaging and in vivo stability studies using [11C]-dimethyl-diphenyl ammonium, a candidate agent for PET-myocardial perfusion imaging.
abstract: BACKGROUND
  PET myocardial perfusion imaging (MPI) holds several advantages over SPECT for diagnosing coronary artery disease. The short half-lives of prevailing PET-MPI agents hamper wider clinical application of PET in nuclear cardiology; prompting the development of novel PET-MPI agents. We have previously reported on the potential of radiolabeled ammonium salts, and particularly on that of [(11)C]dimethyl-diphenyl-ammonium ([(11)C]DMDPA), for cardiac PET imaging. This study was designed to improve the radiosynthesis and increase the yield of [(11)C]DMDPA, characterize more meticulously the kinetics of radioactivity distribution after its injection via micro-PET/CT studies, and further explore its potential for PET-MPI.
  
  
  METHODS
  The radiosynthetic procedure of [(11)C]DMDPA was improved with respect to the previously reported one. The kinetics of radioactivity distribution following injection of [(11)C]DMDPA were investigated in juvenile and young adult male SD rats using microPET/CT, and compared to those of [(13)N]NH3. Furthermore, the metabolic fate of [(11)C]DMDPA in vivo was examined after its injection into rats.
  
  
  RESULTS
  Following a radiosynthesis time of 25-27 min, 11.9 ± 1.1 GBq of [(11)C]DMDPA was obtained, with a 43.7% ± 4.3% radiochemical yield (n = 7). Time activity curves calculated after administration of [(11)C]DMDPA indicated rapid, high and sustained radioactivity uptake in hearts of both juvenile and young adult rats, having a two-fold higher cardiac radioactivity uptake compared to [(13)N]NH3. Accordingly, at all time points after injection to both juvenile and young adult rats, image quality of the left ventricle was higher with [(11)C]DMDPA compared to [(13)N]NH3. In vivo stability studies of [(11)C]DMDPA indicate that no radioactive metabolites could be detected in plasma, liver and urine samples of rats up to 20 min after injection, suggesting that [(11)C]DMDPA is metabolically stable in vivo.
  
  
  CONCLUSIONS
  This study further illustrates that [(11)C]DMDPA holds, at least in part, essential qualities required from a PET-MPI probe. Owing to the improved radiosynthetic procedure reported herein, [(11)C]DMDPA can be produced in sufficient amounts for clinical use.
authors.affiliation: Cyclotron-Radiochemistry-MicroPET Unit, Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Galith
authors.initials: G
authors.lastname: Abourbeh
authors.forename: Darya
authors.initials: D
authors.lastname: Tsvirkun
authors.forename: Eyal
authors.initials: E
authors.lastname: Mishani
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D004355:Drug Stability; D007553:Isotope Labeling; D008297:Male; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D011854:Radiochemistry; D051381:Rats
chemical_list: D002250:Carbon Radioisotopes; D000644:Quaternary Ammonium Compounds
keywords: Carbon-11; Imaging; Myocardium; PET; Perfusion