A new norepinephrine transporter imaging agent for cardiac sympathetic nervous function imaging:: radioiodinated (R)-N-methyl-3(2-iodophenoxy)-3-phenylpropanamine

Changes of the cardiac norepinephrine transporter (NET) have been reported in several cardiac failures. (R)-N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine (MIPP), the 3-phenoxy-3-phenylpropylamine analogue iodinated at the 2-position of the phenoxy ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating the cardiac norepinephrine transporter by single photon emission computed tomography (SPECT). (R)-[I-125]MIPP was synthesized via a halogen exchange reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC) with high radiochemical yield (60%) and high radiochemical purity (> 98%). The binding affinity of (R)-MIPP for cardiac NET was measured in terms of the displacement of [3 H]desipramine and (R)-[I-125]MIPP from binding sites in rat heart membranes. The binding data revealed that the affinity of (R)-MIPP was 5 times that of nisoxetine which is a selective NET inhibitor. In biodistribution studies, (R)-[I-125]MIPP showed a high uptake followed by rapid clearance in the heart. (R)-[I-125] MIPP binding sites were saturable and the administration of nisoxetine and desipramine, selective NET inhibitors, decreased the cardiac accumulation of (R)-[I-125]MIPP. These results suggested that (R)-[I-123]MIPP may be an useful radiopharmaceutical for imaging cardiac sympathetic nervous functions. (C) 2003 Elsevier Inc. All rights reserved.