Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.
(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites.


METHODS
Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma.


RESULTS
NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma.


CONCLUSIONS
In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.
Thackeray
James T
JT
Cardiovascular PET Molecular Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Beanlands
Rob S
RS
Dasilva
Jean N
JN
D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging / Q000378:metabolism*; D000818:Animals; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D004809:Ephedrine