INTRODUCTION: To explore the possible use of positron emission tomography (PET) probes for imaging of I(2)-imidazoline receptors (I(2)Rs) in peripheral tissues, we labeled two new I(2)R ligands, 2-[2-(o-tolyl)vinyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 3.7 nM) and 2-[2-(o-tolyl)ethyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 1.7 nM) with (11)C ([(11)C]metrazoline and [(11)C]TEIMD), respectively, and evaluated these ligands and the recently developed I(2)R ligand 2-[3-fluoro-[4-(11)C]tolyl]-4,5-dihydro-1H-imidazole ([(11)C]FTIMD) by in vivo studies. METHODS: [(11)C]Metrazoline and [(11)C]TEIMD were prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [(11)C]methyl iodide. Their biodistribution in mice was investigated by tissue dissection. In addition, PET scans and metabolite analysis were performed. RESULTS: [(11)C]Metrazoline and [(11)C]TEIMD were successfully synthesized with a suitable radioactivity for injection. In the liver and pancreas expressing I(2)Rs, coinjection with the high-affinity I(2)R ligand, BU224, induced a reduction in the radioactivity level at 30 min after injection of [(11)C]metrazoline and [(11)C]FTIMD. However, the radioactivity level after injection of [(11)C]TEIMD was unchanged. In the PET study, coinjection with BU224 induced a decrease in the radioactivity level in the liver and pancreas after more than 15 min of injection of [(11)C]metrazoline and [(11)C]FTIMD as compared with the results obtained for controls. In metabolite analysis, coinjection with BU224 induced a significant reduction in the percentage of unchanged [(11)C]metrazoline at 30 min after injection as compared with that in the control, although no significant difference was observed in the percentage of unchanged [(11)C]FTIMD. CONCLUSION: [(11)C]Metrazoline may be a more useful PET probe than [(11)C]FTIMD for imaging of I(2)Rs in peripheral tissues.
INTRODUCTION: To explore the possible use of positron emission tomography (PET) probes for imaging of I(2)-imidazoline receptors (I(2)Rs) in peripheral tissues, we labeled two new I(2)R ligands, 2-[2-(o-tolyl)vinyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 3.7 nM) and 2-[2-(o-tolyl)ethyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 1.7 nM) with (11)C ([(11)C]metrazoline and [(11)C]TEIMD), respectively, and evaluated these ligands and the recently developed I(2)R ligand 2-[3-fluoro-[4-(11)C]tolyl]-4,5-dihydro-1H-imidazole ([(11)C]FTIMD) by in vivo studies. METHODS: [(11)C]Metrazoline and [(11)C]TEIMD were prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [(11)C]methyl iodide. Their biodistribution in mice was investigated by tissue dissection. In addition, PET scans and metabolite analysis were performed. RESULTS: [(11)C]Metrazoline and [(11)C]TEIMD were successfully synthesized with a suitable radioactivity for injection. In the liver and pancreas expressing I(2)Rs, coinjection with the high-affinity I(2)R ligand, BU224, induced a reduction in the radioactivity level at 30 min after injection of [(11)C]metrazoline and [(11)C]FTIMD. However, the radioactivity level after injection of [(11)C]TEIMD was unchanged. In the PET study, coinjection with BU224 induced a decrease in the radioactivity level in the liver and pancreas after more than 15 min of injection of [(11)C]metrazoline and [(11)C]FTIMD as compared with the results obtained for controls. In metabolite analysis, coinjection with BU224 induced a significant reduction in the percentage of unchanged [(11)C]metrazoline at 30 min after injection as compared with that in the control, although no significant difference was observed in the percentage of unchanged [(11)C]FTIMD. CONCLUSION: [(11)C]Metrazoline may be a more useful PET probe than [(11)C]FTIMD for imaging of I(2)Rs in peripheral tissues.