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

为了在检测生物活性物质（约100%）时实现更高的灵敏度，抗体、药物、反义寡核苷酸等）并减少放射性废物的处理，短寿命的伽马发射金属放射性核素附着在这样的分子上。选择镓-67（Ga-67，半衰期= 78小时）或铟-111（In-111，半衰期= 2.8天）作为金属放射性核素，并将生物活性物质与去铁胺、二乙烯三胺-五乙酸或异硫氰基苄基-EDTA缀合进行放射性标记。(1)抗体：将抗人生长激素（GH）单克隆抗体与去铁胺（DF）通过双胍-淀粉聚合物间隔物偶联，并用Ga-67标记。使用这种Ga-67-抗GH抗体，可以实现灵敏度提高10倍的免疫放射分析。(2)药物：地高辛，一种需要治疗药物监测的强心苷，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。利用Ga-67-DF-地高辛，成功地进行了地高辛放射免疫分析和心肌Na，K-ATP酶活体显像。3）反义寡核苷酸：将人c-erbB-2反义寡核苷酸5 ′-氨基化后，与异硫氰基苄基-EDTA（IBE）偶联，用In-111标记。In-111-IBE-寡核苷酸即使在人血清中也显示出高稳定性，这表明可能的体内应用。事实上，c-erbB 2 mRNA（+）荷瘤裸鼠的生物分布研究表明，短寿命金属放射性核素不仅可用于体内核医学，而且可用于体外诊断和基础研究。

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.