암세포 표적지향화를 위한 항체-엔도스타틴 융합단백질의 체내동태 및 종양으로의 이행성In Vivo Tumor Cell Distribution of Antibody-Endostatin Fusion Protein forTumor-Specific Targeting and Pharmacokinetics
- Other Titles
- In Vivo Tumor Cell Distribution of Antibody-Endostatin Fusion Protein forTumor-Specific Targeting and Pharmacokinetics
- Authors
- 강영숙; 이나영
- Issue Date
- Dec-2003
- Publisher
- 한국약제학회
- Citation
- 약제학회지, v.33, no.4, pp 5 - 292
- Pages
- 288
- Journal Title
- 약제학회지
- Volume
- 33
- Number
- 4
- Start Page
- 5
- End Page
- 292
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/16253
- ISSN
- 2093-5552
2093-6214
- Abstract
- A novel antitumor agent, antibody-endostatin fusion protein (anti-HER2/neu IgG3C_(H)3-Endostatin, AEFP) formed by genetic engineering procedure from antibody (Ab) which specifically targets to tumor cells and angiogenesis inhibitor, endostain (Endo) that has excellent antitumor effect, minimizes the toxicity of normal cells and selectively kills only tumor cells. The purpose of this study is to evaluate the pharmacokinetic parameters and to analyze the localization of AEFP. After an intravenous injection of 150μl (5μCi)[^(125)I]Ab,[^(125)I] AEFP to mice, blood was collected through retroorbital plexus from 15 min to 2880 min. Following the jugular vein injection of 150μl (10μCi)[^(125)I] Endo, blood was collected by the use of carotid artery cannulation from 0.25 min to 30 min. Cosequently, Endo was very rapidly removed from plasma compartment whiin 30 min. On the other hand, AEFP similar to Ab was slowly cleared from plasma. Also, Endo was metabolized about 40% within 30 min. However, AEFP was shown to metabolize less than 10% within 2880 min. The organ distribution of Endo was in order kidney, lung, spleen. Both Ab and AEFP were localized in order spleen, kidney, liver. Futhermore the tumor/blood distribution ratio of AEFP at 96 hours after injection is about 20 times higher than it of Endo at one hour after injection. In conclusion, theses studies demonstrate that the anti-cancer or suppression of angiogenesis effect of Endo may be improved by the use of AEFP because the longer half life and stability of AEFP is able to selectively target antigens expressed on tumors.
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