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

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.