使用针对细胞间黏附分子-1的铟-111标记抗体早期检测大鼠博来霉素诱导的肺损伤。

Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.

作者信息

Weiner R E, Sasso D E, Gionfriddo M A, Syrbu S I, Smilowitz H M, Vento J, Thrall R S

机构信息

Department of Diagnostic Imaging, University of Connecticut Health Center, Farmington 06030, USA.

出版信息

J Nucl Med. 1998 Apr;39(4):723-8.

PMID:9544689

Abstract

UNLABELLED

We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin.

METHODS

Rats received an intravenous injection of either (111)InaICAM-1 or (111)In-labeled normal mouse IgG ((111)InnmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed. After death, tissue was removed and activity was measured, lungs were cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-1alpha was examined on blood polymorphonuclear leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis.

RESULTS

In rats injected with (111)InaICAM-1, the percent injected dose/organ in lungs both at 4 and 24 hr postbleomycin increased significantly compared to the values in either uninjured rats or rats that received (111)InnmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For (111)InnmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In (111)InaICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood-pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs. Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values.

CONCLUSION

Biodistribution and imaging data demonstrate that (111)InaICAM-1 can detect early acute bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that (111)InICAM-1 uptake is a specific process. This antibody has potential as an early radionuclide detector of acute inflammations.

摘要

未标记

我们研究了一种针对大鼠细胞间黏附分子-1的（111）铟标记的小鼠单克隆抗体（（111）In*aICAM-1）能否在博来霉素处理的大鼠中早期检测到肺损伤。

方法

大鼠静脉注射（111）InaICAM-1或（111）铟标记的正常小鼠IgG（（111）InnmIgG），24小时后进行成像并处死。在处死大鼠前4或24小时通过气管内注射博来霉素诱导肺损伤。处死大鼠后，取出组织并测量活性，将肺组织进行冰冻切片以通过免疫荧光检测ICAM-1的存在，并使用荧光激活细胞分选仪（FACS）分析检测血液多形核白细胞（PMN）上LFA-1α的上调情况。

结果

在注射（111）InaICAM-1的大鼠中，与未受伤大鼠或接受（111）InnmIgG的大鼠相比，博来霉素处理后4小时和24小时肺中的注射剂量百分比/器官均显著增加。在损伤后4小时和24小时，靶/血（T/B）比值分别为8/1和6/1。对于（111）InnmIgG，4小时时的T/B比值为0.5/1，24小时时为0.4/1。在4小时或24小时受伤的（111）InaICAM-1大鼠中，图像很容易与未受伤大鼠区分开来。所有（111）In*nmIgG大鼠的图像仅显示心脏血池和肝脏活性，肺部活性很少。与未受伤的肺相比博来霉素处理的样本中肺ICAM-1免疫荧光强度增加。与对照值相比，损伤后4小时和24小时PMN上LFA-1α的表达分别增加了19%和210%。