Abstract
918
Objectives: The use of in vivo molecular imaging using small animal PET or SPECT has been expected to increase efficiencies in drug discovery and development of CNS drugs. In this study, the neuroprotective effects of two drug candidates to the dopaminergic neuronal damage induced by 6-OHDA in the rat striatum was tested using animal PET.
Methods: Fiteen SD rats were divided into three groups. The rats of each group were orally administrated one of neuroprotective candidates; NeuProtec (100mg/kg bid) or SureCero (10 mg/kg, qd), and normal saline (0.1ml, qd). 6-OHDA was sterotactically placed to the right striatum on 8th day while continuing the medication for additional 14 days. [124I]-CIT PET scans and amphetamine-induced rotation test were conducted. And histological examination was performed after scarifying.
Results: Different FP-CIT uptake in the 6-OHDA lesioned striatum among the groups was observed. The rats treated with NeuProtec showed the relatively higher uptake in the lesioned striatum with lower asymmetry index of the striatal uptake than controls. However, The SureCero group did not showed the difference in FP-CIT uptake. FP-CIT uptake in the striatum was positively correlated with % TH positive cells in the striatum (ρ= 0.73, p=0.02), and also correlated with behavior changes in rotation test (ρ =0.79, p=0.001).
Conclusions: Quantitative microPET images could demonstrate that NeuProtec diminished the dopaminergic neuronal damage by 6-OHDA. No demonstrable effect of SureCero in this study may indicate the possibility of use of suboptimal dosage for protection to 6-OHDA toxicity. Quantitative microPET with small animals could be potential in preclinical evaluation of the effects and dosage in drug discovery.
- Society of Nuclear Medicine, Inc.