Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.
Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.
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DOI：
10.1016/j.nucmedbio.2010.03.010
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Zalutsky MR
中科院分区：
文献类型：
--
作者：
Kato Y;Vaidyanathan G;Kaneko MK;Mishima K;Srivastava N;Chandramohan V;Pegram C;Keir ST;Kuan CT;Bigner DD;Zalutsky MR
PodoPlanin/Aggrus是一种粘蛋白样涎糖蛋白，在恶性胶质瘤中高度表达。据报道，泊多拉宁是一种新的标志物，可以丰富肿瘤起始细胞，这些细胞被认为可以抵抗传统疗法，并与癌症复发有关。本研究的目的是确定抗泊多普宁抗体是否适合作为恶性胶质瘤的靶向放射性核素。用表面等离子体共振和Scatchard分析测定了抗泊多拉宁抗体NZ-1(大鼠IgG2a)的结合亲和力。[131I]SGMIB-NZ-1用~(125)I标记NZ-1，进行双标记内化分析。比较125I-NZ-1和[131I]SGMIB-NZ-1在荷瘤裸鼠体内的组织分布。表面等离子体共振法测得NZ-1的解离常数为1.2×10-10M，Scatchard法测得D397 MG胶质母细胞瘤细胞的解离常数Kd为9.8×10-10M。在LN319胶质母细胞瘤细胞中的双标记内化分析表明，[131I]SGMIB-NZ-1导致细胞内放射性滞留(8h时为初始结合放射性的26.3±0.8%)高于125I-NZ-1(8h时为10.0±0.1%)。同样，荷D2159 MG裸鼠体内肿瘤摄取[131I]SGMIB-NZ-1(24小时39.9±8.8%ID/g)显著高于125I-NZ-1(24小时29.7±6.1%ID/g)。总体结果表明，抗泊多普宁抗体NZ-1值得进一步评估，以抗体为基础的治疗胶质母细胞瘤。
Podoplanin/Aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to be responsible for cancer relapse. The purpose of this study is to determine whether an anti-podoplanin antibody is suitable to target radionuclides to malignant gliomas. The binding affinity of an anti-podoplanin antibody, NZ-1 (rat IgG2a) was determined by surface plasmon resonance and Scatchard analysis. NZ-1 was radioiodinated with 125I using Iodogen [125I-NZ-1(Iodogen)] or N-succinimidyl 4-guanidinomethyl 3-[131I]iodobenzoate ([131I]SGMIB-NZ-1), and paired-label internalization assays of NZ-1 were performed. The tissue distribution of 125I-NZ-1(Iodogen) and that of [131I]SGMIB-NZ-1 were then compared in athymic mice bearing glioblastoma xenografts. The dissociation constant (KD) of NZ-1 was determined to be 1.2 × 10-10 M by surface plasmon resonance, and 9.8 × 10-10 M for D397MG glioblastoma cells by Scatchard analysis. Paired-label internalization assays in LN319 glioblastoma cells indicated that [131I]SGMIB-NZ-1 resulted in higher intracellular retention of radioactivity (26.3 ± 0.8% of initially bound radioactivity at 8 hr) compared to that from the 125I-NZ-1(Iodogen) (10.0 ± 0.1% of initially bound radioactivity at 8 hr). Likewise, tumor uptake of [131I]SGMIB-NZ-1 (39.9 ± 8.8%ID/g at 24 hr) in athymic mice bearing D2159MG xenografts in vivo was significantly higher than that of 125I-NZ-1(Iodogen) (29.7 ± 6.1%ID/g at 24 hr). The overall results suggest that an anti-podoplanin antibody NZ-1 warrants further evaluation for antibody-based therapy against glioblastoma.
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影响因子：
3.5
作者：
Kaneko, Mika Kato;Kato, Yukinari;Osawa, Motoki
通讯作者：
Osawa, Motoki
DOI：
10.1016/j.bbrc.2006.08.171
发表时间：
2006-11-03
影响因子：
3.1
作者：
Kato, Yukinari;Kaneko, Mika Kato;Osawa, Motoki
通讯作者：
Osawa, Motoki
DOI：
10.1073/pnas.92.19.8999
发表时间：
1995-09-12
影响因子：
11.1
作者：
SAGA, T;NEUMANN, RD;WEINSTEIN, JN
通讯作者：
WEINSTEIN, JN
影响因子：
6
作者：
Kunita, Akiko;Kashima, Takeshi G.;Fujita, Naoya
通讯作者：
Fujita, Naoya
影响因子：
--
作者：
Ogasawara, Satoshi;Kaneko, Mika Kato;Kato, Yukinari
通讯作者：
Kato, Yukinari