Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart

Clifford R. Berry, Pradeep K. Garg, Michael R. Zalutsky, R. Edward Coleman, Timothy R DeGrado

Research output: Contribution to journalArticle

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Abstract

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. 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 μM SKF550; (Group 4) DMI + SKF550; (Group 5) SKF550 + 1.0 μM Ro 4-1284; and (Group 6) SKF550 with DMI chase at 30 min (n = 4). 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 (T( 1/4 ) = 5.32 ±. 1.1 min) and slow (T( 1/4 ) = 35.2 ± 9.6 min) components were noted in control hearts. The rapid (T( 1/4 ) = 1.6 ± 0.3 min) and slow (T( 1/4 ) = 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. 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.

Original languageEnglish (US)
Pages (from-to)2011-2016
Number of pages6
JournalJournal of Nuclear Medicine
Volume37
Issue number12
StatePublished - Dec 1996
Externally publishedYes

Fingerprint

Fluorine
Desipramine
2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-2H-benzo(a)quinolizin-2-ol
Radioactivity
Perfusion
4-fluorobenzylguanidine
Control Groups

Keywords

  • catecholamine uptake
  • fluorine-18-PFBG
  • rat heart

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart. / Berry, Clifford R.; Garg, Pradeep K.; Zalutsky, Michael R.; Coleman, R. Edward; DeGrado, Timothy R.

In: Journal of Nuclear Medicine, Vol. 37, No. 12, 12.1996, p. 2011-2016.

Research output: Contribution to journalArticle

Berry, CR, Garg, PK, Zalutsky, MR, Coleman, RE & DeGrado, TR 1996, 'Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart', Journal of Nuclear Medicine, vol. 37, no. 12, pp. 2011-2016.
Berry, Clifford R. ; Garg, Pradeep K. ; Zalutsky, Michael R. ; Coleman, R. Edward ; DeGrado, Timothy R. / Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart. In: Journal of Nuclear Medicine. 1996 ; Vol. 37, No. 12. pp. 2011-2016.
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title = "Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart",
abstract = "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. 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 μM SKF550; (Group 4) DMI + SKF550; (Group 5) SKF550 + 1.0 μM Ro 4-1284; and (Group 6) SKF550 with DMI chase at 30 min (n = 4). 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 (T( 1/4 ) = 5.32 ±. 1.1 min) and slow (T( 1/4 ) = 35.2 ± 9.6 min) components were noted in control hearts. The rapid (T( 1/4 ) = 1.6 ± 0.3 min) and slow (T( 1/4 ) = 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. 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.",
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AU - Coleman, R. Edward

AU - DeGrado, Timothy R

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N2 - 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. 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 μM SKF550; (Group 4) DMI + SKF550; (Group 5) SKF550 + 1.0 μM Ro 4-1284; and (Group 6) SKF550 with DMI chase at 30 min (n = 4). 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 (T( 1/4 ) = 5.32 ±. 1.1 min) and slow (T( 1/4 ) = 35.2 ± 9.6 min) components were noted in control hearts. The rapid (T( 1/4 ) = 1.6 ± 0.3 min) and slow (T( 1/4 ) = 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. 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.

AB - 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. 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 μM SKF550; (Group 4) DMI + SKF550; (Group 5) SKF550 + 1.0 μM Ro 4-1284; and (Group 6) SKF550 with DMI chase at 30 min (n = 4). 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 (T( 1/4 ) = 5.32 ±. 1.1 min) and slow (T( 1/4 ) = 35.2 ± 9.6 min) components were noted in control hearts. The rapid (T( 1/4 ) = 1.6 ± 0.3 min) and slow (T( 1/4 ) = 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. 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.

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