当前位置：
X-MOL 学术
›
Bioconjugate Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Radioligand Therapy of Prostate Cancer with a Long-Lasting Prostate-Specific Membrane Antigen Targeting Agent 90Y-DOTA-EB-MCG
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-06-04 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00292 Zhantong Wang 1 , Orit Jacobson 1 , Rui Tian 1 , Ronnie C. Mease 2 , Dale O. Kiesewetter 1 , Gang Niu 1 , Martin G. Pomper 2 , Xiaoyuan Chen 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-06-04 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00292 Zhantong Wang 1 , Orit Jacobson 1 , Rui Tian 1 , Ronnie C. Mease 2 , Dale O. Kiesewetter 1 , Gang Niu 1 , Martin G. Pomper 2 , Xiaoyuan Chen 1
Affiliation
|
Several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of radiotheranostics for the treatment of prostate cancer. Among them, (((R)-1-carboxy-2-mcercaptoethyl)carbamoyl)-l-glutamic acid (MCG) has been successfully labeled with radioisotopes for prostate cancer imaging. The aim of this study is to conjugate MCG with an albumin binding moiety to further improve the in vivo pharmacokinetics. MCG was conjugated with an Evans blue (EB) derivative for albumin binding and a DOTA chelator. PSMA positive (PC3-PIP) and PSMA negative (PC3) cells were used for both in vitro and in vivo studies. Longitudinal PET imaging was performed at 1, 4, 24, and 48 h post-injection to evaluate the biodistribution and tumor uptake of 86Y-DOTA-EB-MCG. DOTA-EB-MCG was also labeled with 90Y for radionuclide therapy. Besides tumor growth measurement, tumor response to escalating therapeutic doses were also evaluated by immunohistochemistry and fluorescence microscopy. Based on quantification from 86Y-DOTA-EB-MCG PET images, the tracer uptake in PC3-PIP tumors increased from 22.33 ± 2.39%ID/g at 1 h post-injection (p.i.), to the peak of 40.40 ± 4.79%ID/g at 24 h p.i. Administration of 7.4 MBq of 90Y-DOTA-EB-MCG resulted in significant regression of tumor growth in PSMA positive xenografts. No apparent toxicity or body weight loss was observed in all treated mice. Modification of MCG with an Evans blue derivative resulted in a highly efficient prostate cancer targeting agent (EB-MCG), which showed great potential in prostate cancer treatment after being labeled with therapeutic radioisotopes.
中文翻译：
持久性前列腺特异性膜抗原靶向剂90 Y-DOTA-EB-MCG的放射性配体疗法治疗前列腺癌
临床上已经引入了几种靶向前列腺特异性膜抗原（PSMA）的放射性配体，作为治疗前列腺癌的一类新的放射治疗学。其中，（（（R）-1-羧基-2-巯基乙基）氨基甲酰基）-1-谷氨酸（MCG）已成功地用放射性同位素标记以用于前列腺癌成像。这项研究的目的是使MCG与白蛋白结合部分缀合，以进一步改善体内药代动力学。MCG与伊文思蓝（EB）衍生物（用于结合白蛋白）和DOTA螯合剂缀合。PSMA阳性（PC3-PIP）和PSMA阴性（PC3）细胞用于体外和体内研究。在注射后的1、4、24和48 h进行纵向PET成像，以评估其的生物分布和肿瘤吸收86 Y-DOTA-EB-MCG。DOTA-EB-MCG也用90 Y标记用于放射性核素治疗。除肿瘤生长测量外，还通过免疫组织化学和荧光显微镜评估了肿瘤对递增治疗剂量的反应。根据对86张Y-DOTA-EB-MCG PET图像的定量分析，PC3-PIP肿瘤中示踪剂的摄取从注射后（pi）1 h时的22.33±2.39％ID / g增加到峰值40.40±4.79％ pi 24 h时的ID / g 7.4 MBq管理90Y-DOTA-EB-MCG导致PSMA阳性异种移植物中肿瘤生长显着消退。在所有治疗的小鼠中均未观察到明显的毒性或体重减轻。用伊文思蓝衍生物修饰MCG产生了一种高效的前列腺癌靶向剂（EB-MCG），在用治疗性放射性同位素标记后，在前列腺癌的治疗中显示出巨大的潜力。
更新日期：2018-06-04
中文翻译：
持久性前列腺特异性膜抗原靶向剂90 Y-DOTA-EB-MCG的放射性配体疗法治疗前列腺癌
临床上已经引入了几种靶向前列腺特异性膜抗原（PSMA）的放射性配体，作为治疗前列腺癌的一类新的放射治疗学。其中，（（（R）-1-羧基-2-巯基乙基）氨基甲酰基）-1-谷氨酸（MCG）已成功地用放射性同位素标记以用于前列腺癌成像。这项研究的目的是使MCG与白蛋白结合部分缀合，以进一步改善体内药代动力学。MCG与伊文思蓝（EB）衍生物（用于结合白蛋白）和DOTA螯合剂缀合。PSMA阳性（PC3-PIP）和PSMA阴性（PC3）细胞用于体外和体内研究。在注射后的1、4、24和48 h进行纵向PET成像，以评估其的生物分布和肿瘤吸收86 Y-DOTA-EB-MCG。DOTA-EB-MCG也用90 Y标记用于放射性核素治疗。除肿瘤生长测量外，还通过免疫组织化学和荧光显微镜评估了肿瘤对递增治疗剂量的反应。根据对86张Y-DOTA-EB-MCG PET图像的定量分析，PC3-PIP肿瘤中示踪剂的摄取从注射后（pi）1 h时的22.33±2.39％ID / g增加到峰值40.40±4.79％ pi 24 h时的ID / g 7.4 MBq管理90Y-DOTA-EB-MCG导致PSMA阳性异种移植物中肿瘤生长显着消退。在所有治疗的小鼠中均未观察到明显的毒性或体重减轻。用伊文思蓝衍生物修饰MCG产生了一种高效的前列腺癌靶向剂（EB-MCG），在用治疗性放射性同位素标记后，在前列腺癌的治疗中显示出巨大的潜力。
京公网安备 11010802027423号