Orit Jacobson1, Galith Abourbeh, Darya Tsvirkun, Eyal Mishani. 1. Cyclotron-Radiochemistry-MicroPET Unit, Department of Medical Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel.
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.
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.