18F-FECNT的生物分布特性及小动物PET显像研究

Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biedistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received 18F-FECNT were sacri-ficed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β-Carbomethoxy-3β-(4-fluorpbenyl)tropane (β-CFT) at before 18F-FECNT injection. MicroPET scans were performed in beth normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of 18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (%ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 min, respectively, post injection. The selective striatum uptake of 18F-FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro-PET exhibited symmetrical (left/right = 1.00±0.05) and the highest uptake of radioactivity (striatum/cere-helium =2.18±0. 16 at 5- 125 min, n =3). As for the hemiparkinsonian rats, nonsymmetrical unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 (n = 3) vs 1.04 ± 0. 05] and the high-est uptake of radioactivity were also noted. Conclusions The results suggest that 18F-FECNT rapidly pas-ses through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.

Biodistribution and microPET imaging of 18F-FECNT as a dopamine transporter imaging agent