| Japanese |
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| Title | In-111標識モノクローナル抗体の肝細胞内放射能分布に関する検討 |
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| Subtitle | 原著 |
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| Authors | 絹谷清剛*, 横山邦彦*, 渡辺直人*, 嬉野孝子*, 油野民雄*, 利波紀久*, 久田欣一* |
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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 | 26 |
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| Number | 2 |
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| Page | 231-237 |
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| Year/Month | 1989/2 |
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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」 In-111標識モノクローナル抗体(In-111 MoAb)によるradioimmunoscintigraphyの問題点である肝放射能持続の機序解明を目的に, In-111 MoAbの肝細胞内放射能分布について検討を試みた. In-111 MoAb(抗メラノーマ抗体225.28S, IgG2a) 40μCi/10μgをラットに投与後経時的に肝組織をホモジネートし3段階の遠心操作を行った. 肝細胞内放射能は, 早期には主に上清分画に存在したが(61%, 3hr), この分画の放射能は経時的に減少し(21%, 72hr), 代ってリソゾームを含むミトコンドリア分画への放射能の増加が認められた(11%→44%). 一方, 核分画, ミクロゾーム分画はどの時間においてもほぼ一定であった. I-125 MoAbでも同様の検討を行ったが, このような変化は認められず常に一定の分布を示した. 以上より, In-111 MoAbが肝細胞に摂取されたのちに, In-111がリソゾームに貯留することが, 肝放射能持続の原因と考えられた. |
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| Practice | 臨床医学：一般 |
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| Keywords | In-111 monoclonal antibody, Hepatic uptake, Subcellular distribution |
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| English |
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| Title | Subcellular Kinetics of In-111 Monoclonal Antibody in Liver |
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| Authors | Seigo KINUYA, Kunihiko YOKOYAMA, Naoto WATANABE, Takako URESHINO, Tamio ABURANO, Norihisa TONAMI, Kinichi HISADA |
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| Authors(kana) | |
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| Organization | Department of Nuclear Medicin, Kanazawa University, School of Medicine |
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| Journal | The Japanese Journal of nuclear medicine |
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| Volume | 26 |
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| Number | 2 |
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| Page | 231-237 |
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| Year/Month | 1989/2 |
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| Article | Original article |
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| Publisher | THE JAPANESE SOCIETY OF NUCLEAR MEDICINE |
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| Abstract | [Summary] To evaluate the mechanism for prolonged retention of In-111 monoclonal antibody (MoAb) by the liver, we investigated the subcellular kinetics of the In-111 225.28S, an antimelanoma IgG2a. Forty μCi/10 μg of the In-111 MoAb was injected IV into groups of SD rats. The liver was excised at 3, 8, 17, 24, 48 and 72 hr and homogenized with 0.25 M sucrose containing 0.01 M Tris-HCI buffer (pH 7.6). Subcellular fractionation was carried out by 3-step (ultra-)centrifugation. The radioactivity of each fraction including nuclear, mitochondrial (lysosomal), microsomal and supernatant fraction was measured and expressed as a percentage of the total radioactivity of all the fractions. Moreover, the supernatant fraction was assessed by size exclusion HPLC. The supernatant was a predominant fraction of the In-111 radioactivity, 61% at 3 hr, and was decreased with time, 21% at 72 hr (p<0.01), while the activity in the mitochondrial fraction continued to increase from 11% to 44%. As compared to these two fractions, the nuclear and microsomal radioactivities were relatively constant, 10-25%, throughout the study. The HPLC analysis revealed that the supernatant In-111 activity at early time points was mainly eluted with an intact IgG and thereafter this major peak activity was reduced with associated activity peaks found in smaller moiety fractions. To compare the In-111 MoAb with the iodine labeled MoAb, we also investigated the subcellular kinetics of the I-125 MoAb in the same manner. We found that I-125 MoAb did not show the sequential distribution changes found with the In-111 MoAb. Our results demonstrated that the mitochondrial fraction which contained lysosome played an important role in hepatic retention for the In-111 MoAb; once taken up by the liver, the MoAb was metabolized in the supernatant and the In-111 ion was transchelated from DTPA onto the lysosomal substances resulting in prolonged retention by the liver. |
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| Practice | Clinical medicine |
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| Keywords | In-111 monoclonal antibody, Hepatic uptake, Subcellular distribution |
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