title: Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake.
abstract: OBJECTIVE
  Although (11)C-hydroxyephedrine ((11)C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of (11)C-HED PET in small- to medium-sized animals. Furthermore, its relation to (123)I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using (11)C-HED PET, and to compare the retention of (11)C-HED with that of (123)I-MIBG.
  
  
  METHODS
  Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of (11)C-HED and (123)I-MIBG, all animals underwent dynamic (11)C-HED PET for 40 min with arterial blood sampling. The (11)C-HED retention fraction and normalised (11)C-HED activity measured by tissue sampling were compared with those measured by PET.
  
  
  RESULTS
  Both the (11)C-HED retention fraction and the normalised (11)C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p<0.001 and R=0.97282, p<0.001, respectively). Inhibition study by 6-OHDA resulted in a significant reduction in retention (90%) for both (11)C-HED and (123)I-MIBG. Reserpine pretreatment reduced (11)C-HED retention by 50%, but did not reduce (123)I-MIBG retention at 40 min after injection.
  
  
  CONCLUSIONS
  Non-invasive quantitation of cardiac sympathetic innervation using (11)C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both (11)C-HED and (123)I-MIBG are specific for sympathetic neurons, (11)C-HED may be more specific for intravesicular uptake than (123)I-MIBG in some situations, such as that seen in reserpine pretreatment.
authors.affiliation: Department of Cardiology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nomura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsunari
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Murakami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsuya
authors.forename: Junichi
authors.initials: J
authors.lastname: Taki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Chen
authors.forename: Kouji
authors.initials: K
authors.lastname: Kajinami
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000818:Animals; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D019797:3-Iodobenzylguanidine; D004809:Ephedrine