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使用手持式伽马探测探头评估七种抗CX-1肿瘤异种移植单克隆抗体的长期反应性。

An assessment of prolonged reactivity of seven monoclonal antibodies against CX-1 tumor xenografts using a hand-held gamma-detecting probe.

作者信息

Nieroda C A, Siddiqi M A, Hinkle G H, Hill T L, Mojzisik C, Olsen J, Rousseau M, Gersman M, Houchens D P, Sardi A

机构信息

Department of Surgery, Ohio State University College of Medicine, Columbus 43210-1228.

出版信息

J Invest Surg. 1989;2(3):227-40. doi: 10.3109/08941938909057429.

Abstract

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.

摘要

使用手持式γ探测仪(Neoprobe系统),在21天内检测了7种对CX-1肿瘤具有已知反应性的单克隆抗体(MAb)的生物分布和动力学。将28只植入人结肠腺癌CX-1异种移植物的免疫缺陷(无胸腺)裸鼠腹腔注射50微居里的125I标记抗体(每种抗体4只小鼠)。7种单克隆抗体中,4种为抗癌胚抗原(MA、MB、MC和MD),2种为抗TAG 72(B72.3 NCI和B72.3发酵型),1种为抗结直肠癌(17-1A)。每天在肿瘤部位和对侧非肿瘤部位(背景)重复记录探测计数,并计算肿瘤与背景(Tu/Bkg)比值。在第21天处死动物,取出血液、心脏、肝脏、脾脏、肺、肾脏、肠道、肌肉和肿瘤进行γ计数。所有抗体在注射后24小时即可识别肿瘤,且随着时间推移特异性肿瘤定位有所改善。尽管除一种抗体(MB)外所有抗体的Tu/Bkg比值均持续增加,但不同抗体的肿瘤长时间结合模式差异很大。这些数据表明抗体从背景组织中逐渐清除,而标记的单克隆抗体活性在肿瘤中持续存在,导致随着注射后时间的增加肿瘤定位得到改善。

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