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免疫反应性影响放射性标记的抗P97 Fab片段的生物分布和肿瘤靶向性。

Immunoreactivity affects the biodistribution and tumor targeting of radiolabeled anti-P97 Fab fragment.

作者信息

Yokoyama K, Reynolds J C, Paik C H, Sood V K, Maloney P J, Larson S M, Reba R C

机构信息

Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland.

出版信息

J Nucl Med. 1990 Feb;31(2):202-10.

PMID:2313360
Abstract

Hydroxylapatite high performance liquid chromatography was used to prepare two fractions from 125I- Fab 96.5. One fraction (peak 1) had relatively low immunoreactivity (25-38%) and the second fraction (peak 2) had high immunoreactivity (70-81%). Scatchard analysis showed similar affinity constants for the two preparations (2.9 x 10(9) M-1 for peak 1; 3.4 x 10(9) M-1 for peak 2). In biodistribution and imaging studies in athymic mice with human melanoma (FEMX-II) xenografts the high immunoreactivity preparation rapidly cleared from the blood and nontumor organs while retention of radioactivity in the tumor was prolonged. The low immunoreactivity preparation, had slower blood and nontumor organ clearance but faster tumor clearance than the high immunoreactivity fraction. Thus, in these studies highly immunoreactive antibody gave higher tumor to nontumor ratios and enhanced the target to nontarget image contrast.

摘要

采用羟基磷灰石高效液相色谱法从125I-Fab 96.5中制备出两个组分。一个组分(峰1)的免疫反应性相对较低(25%-38%),另一个组分(峰2)具有较高的免疫反应性(70%-81%)。Scatchard分析表明这两种制剂的亲和常数相似(峰1为2.9×10⁹ M⁻¹;峰2为3.4×10⁹ M⁻¹)。在对携带人黑色素瘤(FEMX-II)异种移植物的无胸腺小鼠进行的生物分布和成像研究中,高免疫反应性制剂迅速从血液和非肿瘤器官中清除,而肿瘤中的放射性保留时间延长。低免疫反应性制剂的血液和非肿瘤器官清除速度较慢,但肿瘤清除速度比高免疫反应性组分快。因此,在这些研究中,高免疫反应性抗体产生了更高的肿瘤与非肿瘤比值,并增强了靶标与非靶标图像对比度。

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