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放射性标记抗癌胚抗原抗体及其片段在人体结直肠癌光扫描检测中的应用局限性

Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas.

作者信息

Mach J P, Forni M, Ritschard J, Buchegger F, Carrel S, Widgren S, Donath A, Alberto P

出版信息

Oncodev Biol Med. 1980 Aug;1(1):49-69.

PMID:7279698
Abstract

Fifty-three patients with histologically proven carcinoma were injected with highly purified [131I]-labeled goat antibodies or fragments of antibodies against carcinoembryonic antigen (CEA). Each patient was tested by external photoscanning 4, 24, 36 and 48 h after injection. In 22 patients (16 of 38 injected with intact antibodies, 5 of 13 with F(ab')2 fragments and 1 of 2 with Fab' fragments), an increased concentration of 131I radioactivity corresponding to the previously known tumor location was detected by photoscanning 36-48 h after injection. Blood pool and secreted radioactivity was determined in all patients by injecting 15 min before scanning, [99mTc]-labeled normal serum albumin and free 99mTc04-. The computerized subtraction of 99mTc from 131I radioactivity enhanced the definition of tumor localization in the 22 positive patients. However, in spite of the computerized subtraction, interpretation of the scans remained doubtful for 12 patients and was entirely negative for 19 additional patients. In order to provide a more objective evaluation for the specificity of the tumor localization of antibodies, 14 patients scheduled for tumor resection were injected simultaneously with [131I]-labeled antibodies or fragments and with [125I]-labeled normal goat IgG or fragments. After surgery, the radioactivity of the two isotopes present either in tumor or adjacent normal tissues was measured in a dual channel scintillation counter. The results showed that the antibodies or their fragments were 2-4 times more concentrated in the tumor than in the normal tissues. In addition, it was shown that the injected antibodies formed immune complexes with circulating CEA and that the amount of immune complexes detectable in serum was roughly proportional to the level of circulating CEA.

摘要

53例经组织学证实为癌的患者被注射了高度纯化的[131I]标记的山羊抗癌胚抗原(CEA)抗体或抗体片段。在注射后4、24、36和48小时,对每位患者进行外部光扫描检测。在22例患者中(38例注射完整抗体的患者中有16例,13例注射F(ab')2片段的患者中有5例,2例注射Fab'片段的患者中有1例),在注射后36 - 48小时通过光扫描检测到与先前已知肿瘤位置相对应的131I放射性浓度增加。在所有患者中,在扫描前15分钟注射[99mTc]标记的正常血清白蛋白和游离99mTcO4-来测定血池和分泌的放射性。从131I放射性中计算机化减去99mTc增强了22例阳性患者中肿瘤定位的清晰度。然而,尽管进行了计算机化减法,12例患者的扫描结果解释仍存疑问,另外19例患者的扫描结果完全为阴性。为了对抗体肿瘤定位的特异性提供更客观的评估,14例计划进行肿瘤切除的患者同时被注射了[131I]标记的抗体或片段以及[125I]标记的正常山羊IgG或片段。手术后,在双通道闪烁计数器中测量肿瘤或相邻正常组织中存在的两种同位素的放射性。结果表明,抗体或其片段在肿瘤中的浓度比在正常组织中高2 - 4倍。此外,还表明注射的抗体与循环中的CEA形成免疫复合物,并且血清中可检测到的免疫复合物量大致与循环CEA水平成正比。

相似文献

1
Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas.放射性标记抗癌胚抗原抗体及其片段在人体结直肠癌光扫描检测中的应用局限性
Oncodev Biol Med. 1980 Aug;1(1):49-69.
2
Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.注射来自单克隆抗癌胚抗原抗体的¹²³I标记的Fab或F(ab')₂片段后,通过发射计算机断层扫描检测结肠直肠癌。
J Clin Invest. 1986 Jan;77(1):301-11. doi: 10.1172/JCI112291.
3
Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice.用于定位接种于裸鼠的人结肠癌的抗癌胚抗原单克隆抗体的放射性标记片段。
J Exp Med. 1983 Aug 1;158(2):413-27. doi: 10.1084/jem.158.2.413.
4
[Localization of radiolabeled antibody to carcinoembryonic antigen in patients with gastrointestinal carcinoma].[放射性标记的癌胚抗原抗体在胃肠道癌患者中的定位]
Nihon Geka Gakkai Zasshi. 1986 Mar;87(3):297-306.
5
Immunoscintigraphy of colorectal carcinoma with F (ab')2 fragments of anti-CEA monoclonal antibody.用抗癌胚抗原单克隆抗体F(ab')2片段对结直肠癌进行免疫闪烁显像。
Cancer Detect Prev. 1987;10(5-6):335-45.
6
Tumor localization of radio-labeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation.癌胚抗原放射性标记抗体在癌症患者中的肿瘤定位:一项批判性评估。
N Engl J Med. 1980 Jul 3;303(1):5-10. doi: 10.1056/NEJM198007033030102.
7
Circulating immune complexes in cancer patients receiving goat radiolocalizing antibodies to carcinoembryonic antigen.接受针对癌胚抗原的山羊放射性定位抗体的癌症患者体内的循环免疫复合物。
Cancer Res. 1980 Mar;40(3):497-501.
8
Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.通过抗结肠癌放射性标记单克隆抗体对患者进行肿瘤定位。
Cancer Res. 1983 Nov;43(11):5593-600.
9
Cytokine targeting in tumors using a bispecific antibody directed against carcinoembryonic antigen and tumor necrosis factor alpha.使用抗癌胚抗原和肿瘤坏死因子α的双特异性抗体靶向肿瘤中的细胞因子。
Cancer Res. 1996 Oct 15;56(20):4758-65.
10
Tumor scintigraphy with 131I anti CEA monoclonal antibodies and F(ab')2 in colorectal cancer.131I抗癌胚抗原单克隆抗体及F(ab')2在结直肠癌中的肿瘤闪烁显像
Eur J Nucl Med. 1987;13(3):125-9. doi: 10.1007/BF00289023.

引用本文的文献

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Human anti-self antibodies with high specificity from phage display libraries.来自噬菌体展示文库的具有高特异性的人抗自身抗体。
EMBO J. 1993 Feb;12(2):725-34. doi: 10.1002/j.1460-2075.1993.tb05706.x.
2
Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen.用于检测胃肠道和甲状腺髓样癌的断层闪烁扫描术:使用抗癌胚抗原放射性标记单克隆抗体的首次临床结果
Br Med J (Clin Res Ed). 1982 Nov 20;285(6353):1447-51. doi: 10.1136/bmj.285.6353.1447.
3
Immunoscintigraphy and distribution study of experimental tumours using 131I-labelled anti-fibrinogen antibodies.
使用¹³¹I标记的抗纤维蛋白原抗体对实验性肿瘤进行免疫闪烁显像及分布研究。
Eur J Nucl Med. 1984;9(10):478-81. doi: 10.1007/BF00563173.
4
Radioimmunodetection of cancer: problems and potential.癌症的放射免疫检测:问题与潜力
Br Med J (Clin Res Ed). 1983 Nov 12;287(6403):1402-4. doi: 10.1136/bmj.287.6403.1402.
5
Effect of dose escalation of a monoclonal anti-CEA IgG on tumour localisation and tissue distribution in nude mice xenografted with human colon carcinoma.单克隆抗癌胚抗原IgG剂量递增对人结肠癌裸鼠移植瘤定位及组织分布的影响
Cancer Immunol Immunother. 1986;23(2):107-12. doi: 10.1007/BF00199815.
6
Non-human primate (baboon) anti-carcinoembryonic antigen antibody infusion in patients with metastatic adenocarcinoma. A phase I study.非人灵长类动物(狒狒)抗癌胚抗原抗体输注治疗转移性腺癌患者。一项I期研究。
Cancer Immunol Immunother. 1986;23(2):137-42. doi: 10.1007/BF00199820.
7
Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.注射来自单克隆抗癌胚抗原抗体的¹²³I标记的Fab或F(ab')₂片段后,通过发射计算机断层扫描检测结肠直肠癌。
J Clin Invest. 1986 Jan;77(1):301-11. doi: 10.1172/JCI112291.
8
Monoclonal antibody to an intracellular antigen images human melanoma transplants in nu/nu mice.针对细胞内抗原的单克隆抗体可对裸鼠体内的人类黑色素瘤移植瘤成像。
Proc Natl Acad Sci U S A. 1987 Jun;84(12):4200-4. doi: 10.1073/pnas.84.12.4200.
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Current status of cancer imaging with radiolabeled antibodies.放射性标记抗体在癌症成像中的现状
J Cancer Res Clin Oncol. 1987;113(3):203-8. doi: 10.1007/BF00396374.
10
Metabolizable 111In chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice.可代谢的111铟螯合物偶联抗独特型单克隆抗体用于小鼠淋巴瘤的放射免疫检测
Eur J Nucl Med. 1986;12(9):455-60. doi: 10.1007/BF00254750.