B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 anti...B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.展开更多
汽车内饰的静电吸尘影响车内环境和车内仪器仪表的使用寿命。通过熔融共混的方法制备了汽车内饰用永久抗静电PP材料,从4种导电炭黑中选择一种颗粒状导电炭黑,添加量为18%(质量比),永久抗静电PP表面电阻可达1×106Ω,且无虎皮纹等外...汽车内饰的静电吸尘影响车内环境和车内仪器仪表的使用寿命。通过熔融共混的方法制备了汽车内饰用永久抗静电PP材料,从4种导电炭黑中选择一种颗粒状导电炭黑,添加量为18%(质量比),永久抗静电PP表面电阻可达1×106Ω,且无虎皮纹等外观问题。随着高熔体流动速率PP(K7100)用量的增加,材料的熔体流动速率、拉伸强度、弯曲模量均呈上升趋势,但悬臂梁缺口冲击强度明显下降,由26 k J/m2下降到13 k J/m2。采用多孔硅酸盐作为VOC吸附剂,使永久抗静电PP的乙醛和丙烯醛释放量明显减少,但对于苯系物基本没有效果。当VOC吸附剂添加量达到1. 5%(质量比)时,改性PP的VOC满足主机厂的标准要求。永久抗静电PP注塑生产的汽车内饰门板,在试装车路试过程中,零件的灰尘量得到显著降低。展开更多
基金funded by the National Natural Science Foundation of China(31320103918 and 82104318)Key Research and Development Program of Jiangsu Province(BE2021644)+4 种基金the Jiangsu Innovative and Entrepreneurial Talent Programme(JSSCBS20211568)the Science and Technology Plan of Suzhou(SKJYD2021161 and SKY2022046)Key Project of Jiangsu Provincial Health Commission(zd2021050)the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(GZK1202203)support of Jiangsu Institute of Nuclear Medicine for the ^(89)Zr-PET imaging in this study。
文摘B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor cells.In this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody screening.Micro-positron emission tomography(PET)imaging,biodistribution and pharmacokinetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission computed tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in vivo.Fu rthermore,the pharmacodynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor models.Micro-PET imaging and biodistribution analysis with a gamma counter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid varied.The PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent toxicity.Interestingly,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor growth.Taken together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effective antitumor effects with an ideal safety profile.Therefore,we expect hu4G4 to be an excellent antibody for the development of GBM RIT.
文摘汽车内饰的静电吸尘影响车内环境和车内仪器仪表的使用寿命。通过熔融共混的方法制备了汽车内饰用永久抗静电PP材料,从4种导电炭黑中选择一种颗粒状导电炭黑,添加量为18%(质量比),永久抗静电PP表面电阻可达1×106Ω,且无虎皮纹等外观问题。随着高熔体流动速率PP(K7100)用量的增加,材料的熔体流动速率、拉伸强度、弯曲模量均呈上升趋势,但悬臂梁缺口冲击强度明显下降,由26 k J/m2下降到13 k J/m2。采用多孔硅酸盐作为VOC吸附剂,使永久抗静电PP的乙醛和丙烯醛释放量明显减少,但对于苯系物基本没有效果。当VOC吸附剂添加量达到1. 5%(质量比)时,改性PP的VOC满足主机厂的标准要求。永久抗静电PP注塑生产的汽车内饰门板,在试装车路试过程中,零件的灰尘量得到显著降低。
