RT Journal Article
SR Electronic
T1 PET Study of the Neuroprotective Effect of TRA-418, an Antiplatelet Agent, in a Monkey Model of Stroke
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1931
OP 1936
VO 46
IS 11
A1 Kazuo Umemura
A1 Hideo Tsukada
A1 Takeharu Kakiuchi
A1 Naohiro Yamada
A1 Hirotoshi Matsuura
YR 2005
UL http://jnm.snmjournals.org/content/46/11/1931.abstract
AB The aim of this study was to evaluate the neuroprotective effect of TRA-418, an antiplatelet agent, using PET in a monkey model of stroke. TRA-418 is a nonprostanoid compound with dual action: antagonistic effects on thromboxane A2 receptors and agonistic effects on prostaglandin I2 receptors. Methods: Via a transorbital approach, cynomolgus monkeys underwent a 3-h occlusion of the right middle cerebral artery (MCA), followed by reperfusion and observation for 4 d. Starting 2 h after the MCA occlusion, TRA-418 was administered at low and high doses (6 animals at each dose). Six control animals received a bolus and infusion of drug vehicle after MCA occlusion. Steady-state 15O continuous inhalation was used for assessment of local cerebral blood flow, cerebral metabolic rate of oxygen, and oxygen extraction fraction using high-resolution PET. Five consecutive PET scans (before occlusion; 2 h after occlusion; and 2 h, 24 h, and 4 d after reperfusion) were obtained for each monkey. The extent of the cerebral damage due to ischemia was measured histologically at 4 d after reperfusion. Results: Histologic observation 4 d after MCA occlusion showed that cerebral damage was less (P = 0.05) in animals treated with high-dose TRA-418 than in control animals. Although not affecting cerebral blood flow during the experiments, treatment with TRA-418 significantly (P < 0.05) suppressed reduction of the cerebral metabolic rate of oxygen after reperfusion. Conclusion: Our observations suggest that TRA-418 has neuroprotective action, as displayed in a primate model of stroke using PET monitoring.