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  • Title: Mapping of the cardiac sympathetic nervous system by single photon emission tomography with technetium-99m-labelled fluorobenzylpiperidine derivative (99mTc-FBPBAT): result of a feasibility study in a porcine model and an initial dosimetric estimation in humans.
    Author: Richter S, Schaefer A, Menger MD, Kirsch CM, Samnick S.
    Journal: Nucl Med Commun; 2005 Apr; 26(4):361-8. PubMed ID: 15753796.
    Abstract:
    BACKGROUND: Positron emission tomography (PET) and single photon emission tomography (SPET) offer the most promising tools for the in-vivo assessment of the cardiac autonomic nervous system in humans. However, the clinical application of PET and SPET on a routine basis is severely limited by the lack of widely available selective radiotracers. Technetium-99m-labelled 4-fluorobenzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2-mercapto-2-methyl-propylamino)-piperidine (99mTc-FBPBAT) is a recently developed radiotracer which exhibited marked adrenergic affinity in previous investigations in vascular smooth muscle cells and cardiac myocytes, and in rats. In this study, we have verified these findings in a porcine model, and evaluated the potential of SPET with 99mTc-FBPBAT to assess the adrenergic nervous system of the heart. METHODS: Using a SPET camera, scintigraphic evaluations were carried out in pigs following intravenous injection of 99mTc-FBPBAT. The specificity of the cardiac uptake was determined by pharmacological intervention, using alpha- and beta-adrenoceptor antagonists and adrenergic re-uptake blocker. Whole-body kinetic and radiation absorbed doses were estimated from whole-body scintigraphies in two healthy volunteers. RESULTS: 99mTc-FBPBAT-SPET demonstrated a homogeneous distribution of radioactivity in myocardium of pigs and in humans. The cardiac uptake was specifically suppressed by previous treatment of the animals with metoprolol and prazosin, and was displaceable by norepinephrine. In contrast, the inhibition of radioactivity uptake into the heart was less pronounced after pretreatment with desipramine. The peak radioactivity in blood was determined after 1.5-2 min, followed by a plateau of nearly constant radioactivity from 25-30 min onwards. Within 6 h, more than 35% of the injected activity was excreted in the urine. The effective dose according to International Commission on Radiological Protection Publication 60 (ICRP 60) was 0.0064 mSv.MBq-1 for adults. CONCLUSION: In view of these findings, we conclude that the myocardial uptake of 99mTc-FBPBAT reflects the sympathetic adrenergic nervous system of the heart. The effective dose estimated indicates that the clinical use of 99mTc-FBPBAT results in an acceptable radiation dose in humans. Despite the relatively high radioactivity uptake into the lung and liver, 99mTc-FBPBAT appears to be the first promising Tc-based radiotracer for scintigraphic assessment of the cardiac adrenergic system. This result encourages further development of Tc-based agents for routine SPET studies in humans.
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