【摘要】 为进行¹²⁵I-（S）-（-）-3-碘-2-羟基-6-甲氧基-N-[（1-乙基-2-吡咯烷基）甲基]苯酰胺（IBZM）和¹³¹I-IBZM 的标记及其与体内、外中枢 D2受体结合特性评价,应用过氧乙酸法标记,HPLC 和萃取法分离纯化¹²⁵I-IBZM 和¹³¹I-IBZM,通过体外饱和结合实验、大鼠体内及脑内生物分布、大鼠¹²⁵I-IBZM 脑放射自显影、兔平面显像动态观察,对碘标记 IBZM 与 D2受体的结合特性进行了研究。结果:①¹²⁵I-IBZM 和¹³¹I-IBZM 的标记率分别为84.18%±3.06%、78.50%±3.47%.萃取分离后放化纯度均大于90%;经 HPLC 分离纯化后放化纯度均大于95%。②经 Scatchard 作图示 K_J=0.53±0.06nmol/IL,最大结合量 B_max=466.45±45.88fmol/mg 蛋白质。③大鼠脑放射自显影图像分析示:2小时时¹²⁵I-IBZM 在脑内 D2受体丰富的区域如纹状体等有很高的放射性浓聚,其中纹状体/小脑比值可达6.22±0.48;D2受体的特异性拮抗剂 haloperidol 能阻断¹²⁵I-IBZM 在脑内的浓聚。④¹³¹I-IBZM 全身、脑内分布及兔平面显像显示其在脑内的摄取和滞留较好。表明放射性碘标记 IBZM 与大鼠、兔脑内多巴胺 D2受体的结合具有高亲和力、饱和性和特异性。更多还原

【Abstract】 PURPOSE To study preparation of central nerves system dopamine D2 imaging agent ¹³¹I-IBZM and its preclinical investigation.METHODS Peracetie acid was used as the oxidant for preparing radioiodinated ¹²⁵I-IBZM and ¹³¹I-IBZM,D2 bind- ing properties of IBZM were examined by in vitro binding saturation analysis,rat whole body and regional brain biodistribution, rat brain autoradiograpby and rabbit SPECT static imaging,etc.RESULTS 1.The radiolabelling yields of ¹²⁵I-IBZM and ¹³¹I- IBZM were 84.18%±3.06% and 78.50%±3.47%.The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction.2.Scatchard plot of D2 receptor saturation binding analysis showed: K_d=0.53±0.06nmol/L,B_max=466.45±45.88fmol/mg protein.3.The rat brain autoradiography and analysis showed that there was high ¹²⁵I-IBZM uptake in striatal area 2hr after injection,the striatal/cerebellum ratio was 6.22±0.48;the high ¹²⁵I- IBZM uptake can be blocked by haloperidol——a special dopamine D2 receptor antigonist.4.¹³¹I-IBZM rat biodistribution and rabbit SPECT plannar imaging showed good initial brain uptake and retention,the initial uptake of rat brain was 1.893±0.147% ID/g at 2min and 1.044±0.135% ID/g at 60min.CONCLUSIONS The results showed that the radioiodinated IBZM had high affinity,saturation and specificity to rat’s and rabbit’s central nerves system dopamine D2 receptors.更多还原