Neuronal mapping of the heart with 6-[18F]fluorometaraminol

Wieland, Donald M.; Rosenspire, Karen C.; Hutchins, Gary D.; Dort, Marcian Van; Rothley, Jill; Mislankar, Suresh G.; Lee, Helen T.; Massin, Christopher C.; Gildersleeve, David L.; Sherman, Philip S.; Schwaiger, Markus

doi:10.1021/jm00165a012

Cited by 63 publications

(18 citation statements)

References 4 publications

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“…Following uptake and storage, the tracer is retained in tissue with a long biological half-life. Correlation of tissue ["C]HED retention with tissue norepinephrine content in a canine model of regional cardiac denervation showed a close relationship of both measurements (15,26). The analysis of tissue ["CJHED kinetics has been confined to the left ventricle only.…”

Section: -40% ["C]hed Retention In the Apical Segments Ofgroup Imentioning

confidence: 91%

“…4 catecholamine analogue for PET (16,26). This tracer mimics the neuronal uptake and storage of norepinephrine (15). In contrast to norepinephrine, the tracer is not metabolized in sympathetic nerve terminals by monoamine oxidase (27).…”

Section: -40% ["C]hed Retention In the Apical Segments Ofgroup Imentioning

confidence: 99%

“…This paucity ofdata is a direct result of insufficient techniques for the accurate in vivo evaluation of the autonomic nervous system of the human heart. With the advent of imaging methods that enable the delineation of the sympathetic nerve terminals, the noninvasive assessment of the integrity of the sympathetic nervous system has become possible (15)(16)(17). The guanethidine analogue, 1231-meta-iodobenzylguanidine (MIBG) has been employed in combination with conventional nuclear medicine techniques to characterize the effect of various cardiac diseases on the sympathetic nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…In combination with positron emission tomography (PET), this approach enables the quantitative assessment of regional neuronal tracer retention in the heart (20). Animal studies have shown that regional denervation of the canine heart leads to markedly reduced retention ofthis tracer while perfusion is preserved, demonstrating the specificity ofsympathetic hydroxyephedrine uptake (15). Tracer kinetic modeling is being developed to quantify the regional catecholamine storage capacity of heart tissue (21).…”

Section: Introductionmentioning

confidence: 99%

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Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Schwaiger¹,

Hutchins²,

Kalff³

et al. 1991

J. Clin. Invest.

190

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Positron emission tomography in combination with the newly introduced catecholamine analogue ["Clhydroxyephedrine (["CIHED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [CIqHED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (< 1 yr, 4.4±23 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5±13 yr). ["CIHED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous ["C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of ["CIHED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P < 0.001). In group II patients, ["CWHED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation. (J. Clin. Invest. 1991. 87:1681-1690

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Section: -40% ["C]hed Retention In the Apical Segments Ofgroup Imentioning

confidence: 91%

Section: -40% ["C]hed Retention In the Apical Segments Ofgroup Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Schwaiger¹,

Hutchins²,

Kalff³

et al. 1991

J. Clin. Invest.

190

View full text Add to dashboard Cite

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“…Norepinephrine has been labeled with C-11 ((±)- [ 11 C]NE) [24,25] [32], [ 11 C]phenylephrine [33], [ 11 C]meta-hydroxyephedrine [34], have been developed for PET studies of sympathetic innervation in the heart; however, their use as tracers to study brain NET is limited due to their inability to cross the blood-brain barrier. Several potent NET reuptake inhibitors have been labeled for in vitro or in vivo mapping of brain NET; however, the results were not promising due to their high non-specific bindings.…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of Norepinephrine Transporters

Ding¹,

Lin²,

Logan³

2006

CPD

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Abstract:The involvement of the norepinephrine transporter (NET) in the pathophysiology and treatment of attention deficit hyperactivity disorder (ADHD), substance abuse, neurodegenerative disorders (e.g., Alzheimer's disease (AD) and Parkinson's disease (PD)) and depression has long been recognized. However, many of these important findings have resulted from studies in vitro using postmortem tissues; as of now, these results have never been verified via in vivo methods because brain imaging of NET in living systems has been hampered due to the lack of suitable radioligands. The fact that all three monoamine (dopamine, norepinephrine, and serotonin) transporters (DAT, NET and SERT) are involved in various neurological and psychiatric diseases further emphasizes the need to develop suitable NET ligands so that researchers will be able to probe the contributions of each monoamine transporter system to specific CNS disorders. In this review article, the design and biological evaluation of several radioligands for imaging the brain NET system with PET are discussed. Based on these characterization studies, including C-11 labeled desipramine (DMI), 2-hydroxydesipramine (HDMI), talopram, talsupram, nisoxetine (Nis), oxaprotiline (Oxap), lortalamine (Lort) and C-11 and F-18 derivatives of reboxetine (RB), methylreboxetine (MRB) and their individual (R, R) and (S, S) enantiomers, in conjunction with studies with radiolabeled 4-iodo-tomoxetine and 2-iodo-nisoxetine, we have identified the superiority of (S, S)-[11 C]MRB and the suitability of the MRB analogs as potential NET ligands for PET. In contrast, Nis, Oxap and Lort displayed high uptake in striatum (higher than thalamus). The use of these ligands is further limited by high non-specific binding and relatively low specific signal, as is characteristic of many earlier NET ligands. Thus, to our knowledge, (S, S)-[11 C]MRB remains by far the most promising NET ligand for PET studies.

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