| Japanese |
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| Title | スペーサ含有および非含有二官能性キレート剤を用いた111In標識モノクローナル抗体の比較研究 - (II) 担癌ヌードマウスにおける体内動態の検討 - |
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| Subtitle | 原著 |
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| Authors | 孫保福*, 久田欣一** |
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| Organization | *金沢大学医学部核医学科, **主任:教授 |
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| Journal | 核医学 |
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| Volume | 31 |
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| Number | 5 |
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| Page | 473-487 |
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| Year/Month | 1994/5 |
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| Article | 原著 |
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| Publisher | 日本核医学会 |
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| Abstract | 「要旨」succinimido-EGS-DTPA(diester spacer含有), maleimido-C10-Bz-EDTA(hydrocarbon spacer含有)で111In標識したA7抗体の担癌ヌードマウスにおける体内動態を検討した. これらの結合抗体は, 対照のスペーサを含まないキレート結合抗体より低い正常臓器放射能を示し, 特にC10-Bz-EDTA結合抗体で顕著であった. 肝放射能は, C10-Bz-EDTA結合抗体では投与96時間後まで減少したのに対し, EGS-DTPA結合抗体では投与24時間後以降ほぼ一定の値を示した. シンチグラムでも, C10-Bz-EDTA結合抗体で最もよい腫瘍対正常臓器コントラストが得られた. スペーサを含むキレート結合抗体では, 放射能の体外排泄が促進され, C10-Bz-EDTA結合抗体では, 他のキレート結合抗体と異なり, 主に便中に排泄された. 肝細胞内放射能分布ではEGS-DTPA結合抗体は, C10-Bz-EDTA結合抗体に比べ, リソゾームを含むミトコンドリア分画の放射能が経時的に増加した. 以上より, EGS-DTPA結合抗体の肝放射能の低減は, 血中で解離した111In-DTPAの尿中への排泄により抗体の肝摂取量が低下したためであり, 一方, C10-Bz-EDTA結合抗体の肝放射能低減は肝内で生じた小分子量代謝物の速やかな胆道系排泄の結果であると考えられた. C10-Bz-EDTAを用いることにより, 放射免疫診断における病巣検出能の向上が期待される. |
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| Practice | 臨床医学：一般 |
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| Keywords | Monoclonal antibody, Hydrocarbon spacer, Background, Biodistribution, Radioimmunoscintigraphy. |
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| English |
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| Title | Comparative Studies of 111In-Labeled Monoclonal Antibody Using Spacer-Containing and Non-spacer Bifunctional Chelates : (II) Biodistribution, Metabolism and Excretion In Vivo |
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| Subtitle | Original Articles |
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| Authors | Baofu Sun |
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| Organization | Department of Nuclear Medicine, Kanazawa University School of Medicine |
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| Journal | The Japanese Journal of nuclear medicine |
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| Volume | 31 |
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| Number | 5 |
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| Page | 473-487 |
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| Year/Month | 1994/5 |
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| Article | Original article |
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| Publisher | THE JAPANESE SOCIETY OF NUCLEAR MEDICINE |
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| Abstract | [Summary] Indium-111-labeled A7 monoclonal antibodies using two spacer-containing chelates, succinimido-EGS-DTPA (EGS-DTPA: diester spacer) and maleimido-C10-Bz-EDTA (C10-Bz-EDTA: hydrocarbon spacer) were investigated in human LS180 colon tumor bearing nude mice and were compared with two non-spacer chelates, cyclic DTPA dianhydride (cDTPAA) and isothiocyanatobenzyl-EDTA (SCN-Bz-EDTA). Compared with immunoconjugates using non-spacer chelates, immunoconjugates using spacer-containing chelates, especially C10-Bz-EDTA-A7 showed lower 111In activity in normal organs. The radioactivity in the liver for C10-Bz-EDTA-A7 decreased continuously till 96 hrs postinjection, however, this liver radio-activity for EGS-DTPA-A7 showed little change after 24 hrs. Moreover, in liver subcellular distribution study, EGS-DTPA-A7 showed a higher activity retention in mitochondrial fraction which contained lysosome, a place for metabolizing and storing of 111In labeled antibody, than that of C10-Bz-EDTA-A7. The C10-Bz-EDTA-A7 conjugate demonstrated more preferable tumor-to-non tumor contrast on the scintigrams than that found with other three immunoconjugates. Up to 96 hrs postinjection, tumor bearing nude mice injecting with immunoconjugates using spacer-containing chelates excreted twice radioactivity from whole body than that excreted by using non-spacer chelates. Interestingly, different from other three chelates, C10-Bz-EDTA-A7 were mainly excreted via feces. We conclude that the decrease of radioactivity in normal tissues in the case of EGS-DTPA-A7 was duo to the rapid decrease of activity in the blood, while in the case of C10-Bz-EDTA-A7 it was due to the quickly excreted small metabolite through faces. 111In labeled C10-Bz-EDTA conjugate is superior, at least when conjugated with A7, to other three chelate conjugates used in this study. |
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| Practice | Clinical medicine |
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| Keywords | Monoclonal antibody, Hydrocarbon spacer, Background, Biodistribution, Radioimmunoscintigraphy. |
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