目的:前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)可作为前列腺癌诊断的重要靶点。该研究成功制备了1种新型68Ga标记PSMA小分子抑制剂PSMA11,并根据《中华人民共和国药典》标准进行质量控制,同时探讨该分子影像探针...目的:前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)可作为前列腺癌诊断的重要靶点。该研究成功制备了1种新型68Ga标记PSMA小分子抑制剂PSMA11,并根据《中华人民共和国药典》标准进行质量控制,同时探讨该分子影像探针在前列腺癌动物模型中的靶向显像效果。方法:利用68Ge/68Ga发生器淋洗产生68Ga液,标记PSMA11制备正电子分子探针68Ga-PSMA11;建立符合药典标准的质量标准草案,对药品进行质量控制;利用小动物PET/CT,在人前列腺癌细胞LNCaP的SCID小鼠移植瘤模型上研究68Ga-PSMA11在注射后体内动态分布情况。结果:成功制备获得68GaPSMA11,质量控制符合规定,放射化学纯度大于99%,其在体内除肾脏及膀胱放射性生理性高分布外,在肿瘤部位有较明显特异性浓聚,其余器官组织放射性分布均处于较低水平。结论:68Ga-PSMA11标记方法简便,在体内肿瘤中特异性摄取程度高,是一个理想的正电子型PSMA特异性分子探针。展开更多
Prostate-specific membrane antigen(PSMA) is a useful target for diagnostic and therapeutic applications,and it is demonstrated that ^(68) Ga in conjugation with DKFZPSMA-617 is better than ^(68)Ga-PSMA-1 in biodistrib...Prostate-specific membrane antigen(PSMA) is a useful target for diagnostic and therapeutic applications,and it is demonstrated that ^(68) Ga in conjugation with DKFZPSMA-617 is better than ^(68)Ga-PSMA-1 in biodistribution data after 1 h,but more preclinical data are still required.In this paper,we presented the additional preclinical data for ^(68)Ga-DKFZ-PSMA-617 and relevant aspects of its production.^(68) Ga was obtained from the SnO_2-based ^(68)Ge/ ^(68) Ga generator.Optimum conditions(p H,temperature,time and ligand concentration) for ^(68)Ga-DKFZPSMA-617 preparation were studied.Radiochemical purity of the radiolabeled compound was determined by HPLC and RTLC.After stability assessments,the complex was intravenously injected into rats.HPLC and ITLC characterizations indicated that the radiopharmaceutical could be prepared with radiochemical purity of [96 % and specific activity of 308.3 TBq/mmol at the optimized conditions(p H of 3.5–4,ligand amount of 2.4 nmol,temperature of90–95 C and reaction time of 10 min).Also,the biodistribution data showed no undesirable uptake in nontarget organs at any interval after injection.In fact,the activity is cleaned from blood and excreted rapidly via the kidneys.Generally,this compound can be considered as a wellestablished PET imaging agent.展开更多
Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptide...Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.展开更多
文摘目的:前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)可作为前列腺癌诊断的重要靶点。该研究成功制备了1种新型68Ga标记PSMA小分子抑制剂PSMA11,并根据《中华人民共和国药典》标准进行质量控制,同时探讨该分子影像探针在前列腺癌动物模型中的靶向显像效果。方法:利用68Ge/68Ga发生器淋洗产生68Ga液,标记PSMA11制备正电子分子探针68Ga-PSMA11;建立符合药典标准的质量标准草案,对药品进行质量控制;利用小动物PET/CT,在人前列腺癌细胞LNCaP的SCID小鼠移植瘤模型上研究68Ga-PSMA11在注射后体内动态分布情况。结果:成功制备获得68GaPSMA11,质量控制符合规定,放射化学纯度大于99%,其在体内除肾脏及膀胱放射性生理性高分布外,在肿瘤部位有较明显特异性浓聚,其余器官组织放射性分布均处于较低水平。结论:68Ga-PSMA11标记方法简便,在体内肿瘤中特异性摄取程度高,是一个理想的正电子型PSMA特异性分子探针。
文摘Prostate-specific membrane antigen(PSMA) is a useful target for diagnostic and therapeutic applications,and it is demonstrated that ^(68) Ga in conjugation with DKFZPSMA-617 is better than ^(68)Ga-PSMA-1 in biodistribution data after 1 h,but more preclinical data are still required.In this paper,we presented the additional preclinical data for ^(68)Ga-DKFZ-PSMA-617 and relevant aspects of its production.^(68) Ga was obtained from the SnO_2-based ^(68)Ge/ ^(68) Ga generator.Optimum conditions(p H,temperature,time and ligand concentration) for ^(68)Ga-DKFZPSMA-617 preparation were studied.Radiochemical purity of the radiolabeled compound was determined by HPLC and RTLC.After stability assessments,the complex was intravenously injected into rats.HPLC and ITLC characterizations indicated that the radiopharmaceutical could be prepared with radiochemical purity of [96 % and specific activity of 308.3 TBq/mmol at the optimized conditions(p H of 3.5–4,ligand amount of 2.4 nmol,temperature of90–95 C and reaction time of 10 min).Also,the biodistribution data showed no undesirable uptake in nontarget organs at any interval after injection.In fact,the activity is cleaned from blood and excreted rapidly via the kidneys.Generally,this compound can be considered as a wellestablished PET imaging agent.
基金This study was supported by the National Natural Science Foundation of China(grant numbers:31972644,32272959)the University Synergy Innovation Program of Anhui Province(grant number:GXXT-2019-035)+1 种基金the Jiangsu Provincial Medical Innovation Team(grant number:CXTDA2017024)the leading technology foundation research project of Jiangsu Province(grant number:BK20192005).
文摘Background:The chicken chorioallantoic membrane(CAM)model is a potential alter-native to the mouse model based on the 3R principles.However,its value for deter-mination of the in vivo behaviors of radiolabeled peptides through positron emission tomography(PET)imaging needed investigation.Herein,the chicken CAM tumor models were established,and their feasibility was evaluated for evaluating the imag-ing properties of radiolabeled peptides using a 68Ga-labeled HER2 affibody.Methods:Two human breast cancer cell lines were inoculated into chicken CAM and mice,respectively.The tumor-targeting potential and pharmacokinetic profile of a 68Ga-labeled affibody,68Ga-MZHER,in both tumor models were also determined.Results:The tumor-formation time in chicken CAM model was shorter than that of mouse model.The uptake values of human epithelial growth factor receptor-2(HER2)-positive Bcap37 tumors in chicken CAM and mouse models were 5.36±0.26%ID/g and 5.26±0.43%ID/g at 30 min postinjection of 68Ga-MZHER,respectively.At the same time points,the uptake values of HER2-negative MDA-MB-231 tumors in the chicken CAM models and mouse models were 1.57±0.15%ID/g and 1.67±0.25%ID/g,respectively.Ex vivo biodistribution confirmed that more radioactivity accu-mulated in Bcap37 tumors than in MDA-MD-231 tumors in both CAM and mouse models.Conclusion:In this study,the CAM tumor model was successfully prepared.The chicken CAM model is a novel tool for quickly determining the in vivo properties of radiolabeled peptides targeting biomarkers.It may be beneficial for early monitoring of the therapeutic effect of a new drug through PET imaging with specific peptides.
