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Development of new-type radiommunoassay system with higher sensitivity and lower radioactive waste disposal.

开发灵敏度更高、放射性废物处理更少的新型放射免疫分析系统。

基本信息

批准号：
04557049
负责人：
FUJIBAYASHI Yasuhisa
金额：
$ 4.22万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557049/
关键词：
radioimmunoassay high specific activity metal label gallium Indium antisense oligonucleotide antibody digoxin 高感度ガリウム-67 銅-62

项目摘要

To achieve higher sensitivity in the detection of biologically active substances (ca..antibodies, drugs, antisense oligonucleotides, etc.) and lessen radioactive waste disposal, short-lived gamma emitting metal radionuclide was attached to such molecules. Gallium-67(Ga-67, half life=78hr)or indium-111 (In-111, half life=2.8day) was selected as a metalradionuclide and biologically active substances conjugated with deferoxamine, diethylenetriamine-pentaacetic acid or isothiocyanobenzyl-EDTA were radiolabeled.(1) Antibody : monoclonal anti-human growth hormone (GH) antibody was conjugated with deferoxiamine (DF) through dialdehyde-starch polymer spacer and labeled with Ga-67. Using this Ga-67-anti-GH antibody, immunoradiometric assay with 10 times higher sensitivity could be realized.(2) Drug : digoxin, a cardiac glycoside requireing therapeutic drug monitoring, was labeled with Ga-67 using DF as a bifunctional chelating agent. Ga-67-DF-digoxin has similar affinity to anti-digoxin antibody as well as Na, K-ATPase. Using the Ga-67-DF-digoxin, digoxin-RIA as well as myocardial Na, K-ATPase imaging in vivo.were successfully performed.3) Antisense oligonucleotide : Antisense oligonucleotide against human c-erbB-2 was 5'-aminated and conjugated with isothiocyanobenzyl-EDTA (IBE) and labeled with In-111. In-111-IBE-oligonucleotide showed high stability even in human serum, an indication of possible in-vivo application. In fact, biodistribution study in nude mice bearing c-erbB2 mRNA (+) tumor indicated the sequence selective tumor localization.It was concluded that short-lived metal radionuclide can be used not only for in vivo nuclear medicine, but in vitro diagnosis as well as basic research studies.

为了在生物活性物质的检测中达到更高的灵敏度(ca…抗体、药物、反义寡核苷酸等)和减少放射性废物的处置，短寿命的伽马发射金属放射性核素被附着在这类分子上。选择镓-67（Ga-67，半衰期为78小时）或铟-111 （In-111，半衰期为2.8天）作为金属放射性核素，并对与去铁胺、二乙烯三胺-五乙酸或异硫氰苄酶- edta偶联的生物活性物质进行放射性标记。(1)抗体：单克隆抗人生长激素（GH）抗体通过二醛-淀粉聚合物间隔剂与去铁胺（DF）偶联，用Ga-67标记。使用该ga -67抗gh抗体，可实现灵敏度提高10倍的免疫放射测定。(2)药物：地高辛是一种需要治疗药物监测的心脏糖苷，使用DF作为双功能螯合剂，用Ga-67标记。ga -67- df -地高辛与抗地高辛抗体和Na， k - atp酶具有相似的亲和力。采用ga -67- df -地高辛、地高辛- ria以及心肌Na、k - atp酶在体显像。执行成功。3)反义寡核苷酸：抗人c-erbB-2的反义寡核苷酸经5′胺化，与异硫氰酸obase - edta （IBE）偶联，用In-111标记。in- 111- ibe寡核苷酸即使在人血清中也表现出很高的稳定性，表明可能在体内应用。事实上，在携带c-erbB2 mRNA（+）肿瘤的裸鼠中的生物分布研究表明，序列选择性肿瘤定位。结果表明，短寿命金属放射性核素不仅可用于体内核医学，还可用于体外诊断和基础研究。