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利用新型鼠单克隆抗体抗-HM1.24对重度联合免疫缺陷小鼠体内人浆细胞瘤异种移植物进行定位与成像

Localization and imaging of human plasmacytoma xenografts in severe combined immunodeficiency mice by a new murine monoclonal antibody, anti-HM1.24.

作者信息

Ozaki K, Ozaki S, Kosaka M, Saito S

机构信息

1st Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.

出版信息

Tokushima J Exp Med. 1996 Jun;43(1-2):7-15.

PMID:8885684
Abstract

We have examined the localization in the tumor of anti-HM1.24, a murine monoclonal antibody which is specific for human plasma cell-associated antigen. The biodistribution and imaging were compared in severe combined immunodeficiency mice bearing human plasmacytoma (RPMI 8226) xenografts after intravenous injection of radiolabeled anti-HM1.24. The mean tumor uptake of 1 microCi of 125I-labeled anti-HM1.24 was 2.98% injected dose per g of tissue (%ID/g) at day 1 and increased to 5.50% ID/g at day 4, whereas tumor uptake values of control IgG was always less than 1.36% ID/g. The tumor localization indices ranged between 2.35 and 6.03 at day 1 to 4 after injection. Anti-HM1.24 showed no evidence of targeting to normal tissues except a splenic uptake, however, splenic targeting was abolished by the blocking of Fc receptors in the reticuloendothelium. In most cases, tumor-to-tissue ratios were greater than 2 at day 4, indicative of tumor selectivity for anti-HM1.24. Radioimaging with 10 microCi of 131I-labeled anti-HM1.24 showed that 25% of the total-body count were localized in the tumor and the tumors could be visualized without subtraction techniques at day 4. Furthermore, the penetration and binding of anti-HM1.24 to the tumor cells were confirmed by autoradiographic studies. These findings indicate that anti-HM1.24 is a potent agent for detection and targeting of human plasmacytoma.

摘要

我们检测了抗HM1.24(一种对人浆细胞相关抗原具有特异性的鼠单克隆抗体)在肿瘤中的定位。在静脉注射放射性标记的抗HM1.24后,对携带人浆细胞瘤(RPMI 8226)异种移植物的严重联合免疫缺陷小鼠的生物分布和成像进行了比较。1微居里的125I标记抗HM1.24在第1天的平均肿瘤摄取量为每克组织2.98%注射剂量(%ID/g),并在第4天增加到5.50% ID/g,而对照IgG的肿瘤摄取值始终低于1.36% ID/g。注射后第1至4天,肿瘤定位指数在2.35至6.03之间。抗HM1.24除了脾脏摄取外,没有显示出靶向正常组织的证据,然而,网状内皮系统中Fc受体的阻断消除了脾脏靶向。在大多数情况下,第4天时肿瘤与组织的比率大于2,表明抗HM1.24对肿瘤具有选择性。用10微居里的131I标记抗HM1.24进行放射性成像显示,全身计数的25%位于肿瘤中,并且在第4天时无需减法技术即可观察到肿瘤。此外,放射自显影研究证实了抗HM1.24对肿瘤细胞的穿透和结合。这些发现表明,抗HM1.24是检测和靶向人浆细胞瘤的有效试剂。

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