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Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart.
- Source :
-
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 1996 Dec; Vol. 37 (12), pp. 2011-6. - Publication Year :
- 1996
-
Abstract
- Unlabelled: Para-[18F]fluorobenzylguanidine ([18F]PFBG) is a newly developed tracer for imaging myocardial sympathetic neuronal innervation. This study investigated the uptake and retention mechanisms of [18F]PFBG in perfused, isolated rat heart.<br />Methods: Fluorine-18-PFBG was administered to working rat hearts within the perfusion medium at a constant activity concentration (1.5-2 MBq/liter) for 8 min, followed by a washout period (50 min). External scintillation probes with coincidence detection circuitry were used to measure myocardial radioactivity. Six groups of hearts (n = 6, except in Group 6) were studied: (Group 1) control; (Group 2) 100 nM desipramine (DMI); (Group 3) 0.8 microM SKF550; (Group 4) DMI + SKF550; (Group 5) SKF550 + 1.0 microM Ro 4-1284; and (Group 6) SKF550 with DMI chase at 30 min (n = 4).<br />Results: Groups 2, 3 and 4 showed a mean reduction of 19% (uptake-1 blockade), 58% (uptake-2 blockade) and 95% (uptake-1 and uptake-2 blockade) in uptake rates, respectively, compared with control (p < 0.01). A further 33% reduction in the uptake rate was noted with vesicular transport inhibition (Group 5 compared with 3, p = 0.054). Biphasic clearance consisting of rapid (T1/2 = 5.32 +/- 1.1 min) and slow (T1/2 = 35.2 +/- 9.6 min) components were noted in control hearts. The rapid (T1/2 = 1.6 +/- 0.3 min) and slow (T1/2 = 10.9 +/- 1.4 min) clearance rates were accelerated (p < 0.0001) in Group 5 compared to control. DMI chase conditions (Group 6) caused an inhibition of [18F]PFBG washout (p = 0.004) suggesting a role for reverse transport through the uptake-1 carrier.<br />Conclusion: Fluorine-18-PFBG is specifically accumulated by sympathetic nerve terminals. However, further work is recommended in humans to evaluate the potential implications of specific extraneuronal uptake of [18F]PFBG through the uptake-2 mechanism.
- Subjects :
- 2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- pharmacology
Animals
Desipramine pharmacology
Female
Fluorenes pharmacology
Heart drug effects
Heart innervation
Hemodynamics drug effects
In Vitro Techniques
Radionuclide Imaging
Rats
Rats, Sprague-Dawley
Sympathetic Nervous System diagnostic imaging
Sympathetic Nervous System metabolism
Fluorobenzenes pharmacokinetics
Guanidines pharmacokinetics
Heart diagnostic imaging
Subjects
Details
- Language :
- English
- ISSN :
- 0161-5505
- Volume :
- 37
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 8970525