| Japanese |
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| Title | 癌の免疫シンチグラフィにおける高免疫活性モノクローナル抗体の有用性に関する実験的研究 - (II) 腫瘍集積性に及ぼすモノクローナルの免疫活性の影響 - |
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| Subtitle | 原著 |
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| Authors | 横山邦彦* |
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| Organization | *金沢大学医学部核医学科 |
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| Journal | 核医学 |
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| Volume | 25 |
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| Number | 1 |
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| Page | 61-70 |
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| Year/Month | 1988/1 |
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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」抗体の体内動態および腫瘍集積性に対する, 放射性核種標識モノクローナル抗体の免疫活性(IR)の影響を検討する目的で, hydroxylapatite高速液体クロマトグラフィにより分離・精製された, IRの異なる抗体F ab 96.5を用いて動物実験を行った. 担癌ヌードマウスでの体内分布およびイメージング実験の結果から, IRのより高い抗体は, 腫瘍内で長く安定に留まり, かつ血液等の非腫瘍組織から速やかに消失することが示された. それゆえに高い腫瘍対非腫瘍組織の放射能比が得られ, 画像上のコントラスト向上にも大きく貢献した. この結果は診断ばかりでなく治療においても, 高IR抗体の使用が正常組織の被曝線量を軽減させる点で有用と考えられた. さらにIRの低下によって抗体の体内分布が大きく変化し, 腫瘍集積性も不良となるため, 癌の免疫検出法の再現性を論ずる際, IRの検討が不可欠であると考えられた. |
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| Practice | 臨床医学：一般 |
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| Keywords | Radioimmunoscintigraphy, Immunoreactivity, Pharmacokinetics, Tumor targeting, F ab 96.5. |
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| English |
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| Title | Advantage of Highly Immunoreactive Monoclonal Antibodies in Radioimmunoscintigraphy for Tumor Detection : (II) Effect of Immunoreactivity on Biodistribution of Monoclonal Antibodies |
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| Subtitle | Original Articles |
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| Authors | Kunihiko YOKOYAMA |
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| Authors(kana) | |
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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 | 25 |
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| Number | 1 |
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| Page | 61-70 |
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| Year/Month | 1988/1 |
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| Article | Original article |
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| Publisher | THE JAPANESE SOCIETY OF NUCLEAR MEDICINE |
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| Abstract | [Summary] There is theoretically a potential benefit in using a highly immunoreactive monoclonal antibody. The effect of immunoreactivity (IR) on the antibody biodistribution, however, has not yet been described in detail. Thus, this study was designed to investigate the effect of IR on the biodistribution in an animal model. The hydroxylapatite high performance liquid chromatography (HA-HPLC) system has been tested and confirmed to separate the F ab 96.5, an anti melanoma p97 antigen, into high and low IR fractions. 125I-F ab 96.5 preparations with a different IR were administered to groups of nude mice bearing FEM-XII human skin melanoma xenografts for biodistribution and imaging studies. The biodistribution data showed that the high IR antibody improved tumor targeting by increasing activity ratios of tumor to non tumor tissue; the mechanism for the increased tumor to non tumor ratios was increased tumor activity uptake and prolonged tumor activity retention with associated rapid clearance from the blood and non tumor sites. The imaging study visually supported the results obtained in the biodistribution study; the high IR antibody demonstrated better and earlier tumor delineation and the tumor to non tumor contrast continued to improve with time. In this model system, where the whole body clearance rate was the same for the high IR and low IR preparations, the overall antibody metabolism and excretion were not significantly dependent on IR. Therefore, the effect of IR is to alter the distribution of antibody between tumor and blood, with high IR having increased tumor activity and reduced blood activity (consequently reduced non tumor organ activity). This would also be beneficial for therapeutic use of radiolabeled antibodies, since high IR antibodies can minimize undesirable radiation exposure to normal organs. In conclusion, high IR antibodies are essential for optimal tumor targeting. |
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| Practice | Clinical medicine |
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| Keywords | Radioimmunoscintigraphy, Immunoreactivity, Pharmacokinetics, Tumor targeting, F ab 96.5. |
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