放射性标记的单克隆抗体的体外表征特定前列腺特异性膜抗原的细胞外的领域。

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Smith-Jones点,Vallabahajosula年代,戈德史密斯SJ,纳瓦罗V,猎人CJ, Bastidas D,打捆机NH

放射性标记的单克隆抗体的体外表征特定前列腺特异性膜抗原的细胞外的领域。

癌症研究》2000年9月15日,60 (18):5237 - 43。

PubMed ID

11016653 (在PubMed

]

文摘

前列腺特异性膜抗原(PSMA)是一个良好的细胞表面抗原表达的几乎所有前列腺癌(PCas)。已成功目标PSMA体内与(111)以标记7 e11单克隆抗体(mAb;ProstaScint;Cytogen,普林斯顿,纽约),结合PSMA的胞内抗原决定基。这项工作报告三个最近的体外表征发达马伯绑定(PSMAext) PSMA的细胞外的领域。小鼠马伯J415、J533 J591和7 e11放射性标记的131我和评估在竞争和饱和绑定与来自LNCaP基质细胞的研究。J415和J591共轭1,4,7,10-tetraazacyclododecane-N N, N, N”-tetraacetic酸贴上(111)。的吸收和细胞处理这些抗体在可行的LNCaP细胞进行评估。所有四个马伯可以贴上131我350兆贝可/毫克到一个特定的活动没有或几乎没有明显损失的免疫反应性。竞争分析表明J415 PSMAext抗原和J591争夺绑定。 J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. mAb 7E11 did not inhibit the binding of J415, J533, or J591 (or vice versa), consistent with earlier work that these latter mAbs bind PSMAext whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affinity (Kds 1.76 and 1.83 nM), whereas J533 had a lower affinity (Kd, 18 nM). In parallel studies, all four mAbs bound to a similar number of PSMA sites expressed by permeabilized cells (1,000,000-1,300,000 sites/cell). In parallel studies performed with viable LNCaP cells, J415, J533, and J591 bound to a similar number of PSMA sites (i.e., 600,000-800,000 sites/cell), whereas 7E11 bound only to a subpopulation of the available PSMA sites (95,000 sites/cell). This apparent binding of 7E11 to viable cells can be accounted for by a 5-7% subpopulation of permeabilized cells produced when the cells were trypsinized and suspended. Up to five DOTA chelates could be bound to either J415 or J591 without compromising immunoreactivity. A comparison of the cellular uptake and metabolic processing of the 131I- and (111)In-labeled antibodies showed a rapid elimination of 131I from the cell and a high retention of (111)In. All four mAbs recognized and bound to similar numbers of PSMAs expressed by ruptured LNCaP cells (i.e., the exposed intracellular and extracellular domains of PSMA). By comparison to J415 and J591, J533 had a lower binding affinity. Both J415 and J591 recognized and bound to the same high number of PSMAs expressed by intact LNCaP. By contrast, 7E11 bound to fewer sites expressed by intact LNCaP cells (i.e., the exposed extracellular domain of PSMA). Both J415 and J591 are promising mAbs for the targeting of viable PSMA-expressing tissue with diagnostic and therapeutic metallic radionuclides.

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Capromab pendetide	谷氨酸羧肽酶2	蛋白质	人类	是的	其他/未知	细节