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为进行~(125)I-(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~(131)I-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~(125)I-IBZM 和~(131)I-IBZM,通过体外饱和结合实验、大鼠体内及脑内生物分布、大鼠~(125)I-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:①~(125)I-IBZM 和~(131)I-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~(125)I-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~(125)I-IBZM 在脑内的浓聚。④~(131)I-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。
In order to carry out the synthesis of ~ (125) I- (S) - (-) - 3-iodo-2-hydroxy-6-methoxy-N - [(1-ethyl-2-pyrrolidinyl) methyl] (IBZM) and ~ (131) I-IBZM and their association with D2 receptor in vivo and in vitro were evaluated by using peracetic acid method, HPLC and extraction method to separate and purify 125I-IBZM and ~ 131 I-IBZM. The binding of IBZM to D2 receptor (I-IBZM) was detected by in vitro saturation binding assay, biodistribution in vivo and in vivo in rats, brain autoradiography in 125I- The binding properties were studied. Results: The labeling rates of ~ (125) I-IBZM and ~ (131) I-IBZM were 84.18% ± 3.06% and 78.50% ± 3.47%, respectively.The radiochemical purity after extraction was over 90% Post-radiochemical purity were greater than 95%. ② By Scatchard plot K_J = 0.53 ± 0.06nmol / IL, the maximum binding amount B max = 466.45 ± 45.88fmol / mg protein. (3) Image analysis of rat brain autoradiogram showed that ~ (125) I-IBZM was highly radioactively concentrated in D2 receptor-rich areas such as the striatum in the brain at 2 hours, and the ratio of striatum to cerebellum Up to 6.22 ± 0.48; haloperidol, a specific antagonist of D2 receptor, can block the aggregation of 125 I-IBZM in the brain. ④ ~ (131) I-IBZM systemic, intracerebral distribution and planar imaging of the rabbit showed good ingestion and retention in the brain. The results showed that radiolabeled IBZM had high affinity, saturation and specificity in binding to dopamine D2 receptor in rat and rabbit brain.