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J Nucl Med. 2008; 49 (Supplement 1):33P
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Cardiovascular: Basic Science

Small Animal Imaging

In vivo PET imaging of presynaptic sympathoneuronal mechanisms in the rat heart

Dnyanesh Tipre1, James Fox1, Daniel Holt1, Gilbert Green1, Jianhua Yu1, Martin Pomper1, Robert Dannals1 and Frank Bengel1

1 Johns Hopkins Medical Institutions, Baltimore, Maryland

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Objectives: To determine the translational potential of cardiac sympathetic neuronal imaging from rodents to humans, we characterized the rat heart using tracers that reflect different mechanisms: [11C]hydroxyephedrine (HED; tracer of neuronal transport with stable uptake/no washout in healthy humans), [11C]epinephrine (EPI; tracer of vesicular storage with stable uptake/no washout in humans), and [11C]phenylephrine (PHEN; tracer of vesicular leakage and intraneuronal metabolism with initial uptake/subsequent washout in humans).

Methods: Using a GE eXplore Vista small animal PET system, healthy male Wistar rats were studied at baseline, following despiramine pretreatment (DMI block), and with DMI injection 15min after tracer delivery (DMI chase). 60min dynamic scans of the heart were obtained under general anesthesia.

Results: At baseline, HED showed high myocardial uptake and sustained retention; EPI showed moderate uptake and significant biphasic washout; PHEN showed moderate uptake and monoexponential washout. Average left ventricular retention index was 7.38±0.72, 4.24±0.59, and 3.43±0.45%/min and washout rate was 0.13±0.23, 0.50±0.24 and 1.13±0.35%/min for HED, EPI and PHEN, respectively. DMI block decreased myocardial uptake of all tracers by >90%. The DMI chase resulted in increased washout only for HED.

Conclusions: Kinetics of HED in rat myocardium were similar to humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN was encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology to humans.





This Article
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Right arrow Email this article to a friend
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Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
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Right arrow Articles by Tipre, D.
Right arrow Articles by Bengel, F.
PubMed
Right arrow Articles by Tipre, D.
Right arrow Articles by Bengel, F.