放射性药物作为一种安全有效的治疗方法正在被越来越多的用于不同类型肿瘤的治疗研究中,通常使用优先与癌细胞结合或通过生理机制积累的药物到达全身或局部病灶,之后通过发射射线对病灶进行辐照以达到杀死癌细胞的效果,此外这些核素能...放射性药物作为一种安全有效的治疗方法正在被越来越多的用于不同类型肿瘤的治疗研究中,通常使用优先与癌细胞结合或通过生理机制积累的药物到达全身或局部病灶,之后通过发射射线对病灶进行辐照以达到杀死癌细胞的效果,此外这些核素能发射可成像的光子,从而可以无创地观察治疗药物的生物分布。放射性核素偶联药物(radionuclide drug conjugates,RDC)结合了精准靶向和强效杀伤两方面的优势,用携带放射性核素有效载荷的特异性单克隆抗体靶向癌细胞,将能量集中释放在细胞直径几倍的范围内,杀死癌细胞的同时最大程度地限制对肿瘤细胞附近正常组织细胞的损害,疗效良好、不良反应小、能够延长患者生存期,对于晚期肿瘤治疗至关重要。展开更多
The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted...The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.展开更多
The relationship between dopamine D2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra(SN) an...The relationship between dopamine D2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra(SN) and ventral tegmental area(VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125I-IBZM ex-vivo autoradiography analysis and 99mTc-HM-PAO regional cerebral biodistribution were used to evaluate D2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and seudo-operated group, striatum/cerebellum 125I-IBZM uptake ratio was 8.04+-0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the seudo-operated group(p <0.05), 30.11+-4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn’t show significant difference between bilateral brain cortex area(p >0.05). These results indicated that in the 6- OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental bend-parkinsonism.展开更多
文摘放射性药物作为一种安全有效的治疗方法正在被越来越多的用于不同类型肿瘤的治疗研究中,通常使用优先与癌细胞结合或通过生理机制积累的药物到达全身或局部病灶,之后通过发射射线对病灶进行辐照以达到杀死癌细胞的效果,此外这些核素能发射可成像的光子,从而可以无创地观察治疗药物的生物分布。放射性核素偶联药物(radionuclide drug conjugates,RDC)结合了精准靶向和强效杀伤两方面的优势,用携带放射性核素有效载荷的特异性单克隆抗体靶向癌细胞,将能量集中释放在细胞直径几倍的范围内,杀死癌细胞的同时最大程度地限制对肿瘤细胞附近正常组织细胞的损害,疗效良好、不良反应小、能够延长患者生存期,对于晚期肿瘤治疗至关重要。
基金ProjectsupportedbytheNationalNinth FivePlanKeyProjectFoundation No 96 90 2 0 1 2 5
文摘The distribution of ^(125)I recombinant E. coli L-asparaginase in tissues ororgans and the excretion in urine, feces and bile were studied with in vivo radioactive tracertechnique. The amount of radioactivity excreted in urine, feces and bile within 24 h afterintravenous administration of ^(125)I recombinant E. col L-asparaginase to rats was 68.95% ,4.44%and 5.36% of the dose respectively. ^(125)I recombinant E. coli L-asparaginase in plasma samples wasdetermined. The levels of structural intact molecule in plasma samples were evaluated by SDS-PAGEand bio-imaging analyzer system. Pharmacokinetic parameters were assessed with a model-dependentmethod. The concentration-time curves of recombinant E. coli L-asparaginase after intravenousinjection at 1 250 IU·kg^(-1), 2 500, IU·kg^(-1), 5 000 IU·kg^(-1) to rats were consistent withthe two-compartment model. The first and terminal elimination t_(1/2) were 0.52 ~ 0.63 h and 2.39 ~2.76 h respectively. AUC was linearly related to the doses. The results of distribution in tissuesor organs and excretion in urine suggested that the metabolites of the enzyme were cleared bymechanisms of urinary excretion. Pharmacokinetics parameters of recombinant E. coli L- asparaginasein rats are warranted for the design of future clinical trials.
文摘The relationship between dopamine D2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra(SN) and ventral tegmental area(VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125I-IBZM ex-vivo autoradiography analysis and 99mTc-HM-PAO regional cerebral biodistribution were used to evaluate D2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and seudo-operated group, striatum/cerebellum 125I-IBZM uptake ratio was 8.04+-0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the seudo-operated group(p <0.05), 30.11+-4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn’t show significant difference between bilateral brain cortex area(p >0.05). These results indicated that in the 6- OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental bend-parkinsonism.
