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Radiolabeled phenethylguanidines: novel imaging agents for cardiac sympathetic neurons and adrenergic tumors.

ABSTRACT: The norepinephrine transporter (NET) substrates [123I]-m-iodobenzylguanidine (MIBG) and [11C]-m-hydroxyephedrine (HED) are used as markers of cardiac sympathetic neurons and adrenergic tumors (pheochromocytoma, neuroblastoma). However, their rapid NET transport rates limit their ability to provide accurate measurements of cardiac nerve density. [11C]Phenethylguanidine ([11C]1a) and 12 analogues ([11C]1b-m) were synthesized and evaluated as radiotracers with improved kinetics for quantifying cardiac nerve density. In isolated rat hearts, neuronal uptake rates of [11C]1a-m ranged from 0.24 to 1.96 mL min-1 (g wet wt)-1, and six compounds had extremely long neuronal retention times (clearance T1/2 > 20 h) due to efficient vesicular storage. Positron emission tomography (PET) studies in nonhuman primates with [11C]1e, N-[11C]guanyl-m-octopamine, which has a slow NET transport rate, showed improved myocardial kinetics compared to HED. Compound [11C]1c, [11C]-p-hydroxyphenethylguanidine, which has a rapid NET transport rate, avidly accumulated into rat pheochromocytoma xenograft tumors in mice. These encouraging findings demonstrate that radiolabeled phenethylguanidines deserve further investigation as radiotracers of cardiac sympathetic innervation and adrenergic tumors.

SUBMITTER: Raffel DM

PROVIDER: S-EPMC2625310 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Radiolabeled phenethylguanidines: novel imaging agents for cardiac sympathetic neurons and adrenergic tumors.

Raffel David M DM Jung Yong-Woon YW Gildersleeve David L DL Sherman Phillip S PS Moskwa James J JJ Tluczek Louis J LJ Chen Wei W

Journal of medicinal chemistry 20070410 9

The norepinephrine transporter (NET) substrates [123I]-m-iodobenzylguanidine (MIBG) and [11C]-m-hydroxyephedrine (HED) are used as markers of cardiac sympathetic neurons and adrenergic tumors (pheochromocytoma, neuroblastoma). However, their rapid NET transport rates limit their ability to provide accurate measurements of cardiac nerve density. [11C]Phenethylguanidine ([11C]1a) and 12 analogues ([11C]1b-m) were synthesized and evaluated as radiotracers with improved kinetics for quantifying card ...[more]

PMID: 17419605

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Radiolabeled phenethylguanidines: novel imaging agents for cardiac sympathetic neurons and adrenergic tumors.

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Radiolabeled phenethylguanidines: novel imaging agents for cardiac sympathetic neurons and adrenergic tumors.

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