Abstract 17610: Noninvasive Assessment with N-Benzyl-N-[11C]Methyl-2-(7-Methyl-8-oxo-2-Phenyl-7,8-Dihydro-9H-Purin-9-yl)Acetamide ([11C]DAC) Delineates Dynamic Interaction Between Brain and Heart as Well as Local Denervation Status After Cardiac Injury in Rats

Abstract

The central nervous system is thought to influence regulation of the cardiovascular system in response to signals from peripheral tissues, but our understanding of the molecular mechanisms involved is still quite limited. Translocator protein (TSPO)(18 kDa), formerly known as peripheral-type benzodiazepine receptor, is known to increase its local expression after brain or peripheral nerve injuries. Previous studies also reported up-regulation of TSPO(18kDa) in the heart after electric shock on brain, suggesting a role in dynamic interaction between brain and periphery under specific conditions. As a novel, specific positron emission tomography (PET) ligand for TSPO(18kDa), we previously developed N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) in rodent models. These led us to attempt to elucidate temporal profiles of TSPO (18kDa) expression among organs following cardiac injury. To that end, we treated basal anterior myocardium with phenol or saline. We injected [11C]DAC into tail vein on day8 and day50 after operation, respectively. On day8, Phenol-treated rats showed decreased [11C]DAC uptake at the apical anterior area of the heart, contrasting with rather conserved uptake at the non-treated, posterior and the phenol-smeared, basal anterior area. On the other hand, sham-operated rats showed decreased [11C]DAC uptake almost uniformly around the heart. Close correlation was found in [11C]DAC uptake between medulla-to-spinal cord ratio and posterior heart in phenol-treated rats (r = 0.913, p < 0.01). On day50, impaired uptake was thoroughly recovered to the control level in both rats. Consistent with this, we found no difference in 123I-MIBG washout ratio, ejection fraction or blood pressure between them. These results suggests that temporal change in [11C]DAC uptake reflects not only local activity of the cardiac autonomic nerves in response to injury or unexpected neurotomy, but dynamic interaction between brain and heart. In conclusion, TSPO(18kDa) imaging with [11C]DAC can be a promising way to delineate dynamic interactions between central nervous system and the heart, as well as to depict temporal changes of local denervation status in the heart after cardiac injury.