Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake.
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.
Nomura
Yusuke
Y
Department of Cardiology, Kanazawa Medical University, Ishikawa, Japan.
Matsunari
Ichiro
I
Takamatsu
Hiroyuki
H
Murakami
Yoshihiro
Y
Matsuya
Takahiro
T
Taki
Junichi
J
Nakajima
Kenichi
K
Nekolla
Stephan G
SG
Chen
Wei-Ping
WP
Kajinami
Kouji
K
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
D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D019797:3-Iodobenzylguanidine; D004809:Ephedrine