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一种通过放射性标记淀粉样蛋白亲和肽 p5 定量外周组织淀粉样蛋白负荷的新方法。

A novel method for quantifying peripheral tissue amyloid load by using the radiolabeled amyloidophilic peptide, p5.

机构信息

Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA.

出版信息

Amyloid. 2013 Mar;20(1):21-6. doi: 10.3109/13506129.2012.757216. Epub 2013 Jan 17.

Abstract

Quantitation of peripheral amyloid deposits by non-invasive molecular imaging can be useful for diagnosis, prognostication and monitoring response to therapy. In order to obtain reliable quantitative data, it is necessary to show a linear positive correlation between the uptake of the molecular probe and the tissue amyloid load. The transgenic H-2/IL-6 mouse model of AA amyloidosis was used to generate animals with varied stages of visceral amyloid disease. The mice were injected with 125I-labeled peptide p5 and tissues analyzed 2 h post-injection using Congo red (CR) staining, radioisotope biodistribution and micro-autoradiography (ARG). Micro-ARG confirmed that 125I-p5 was deposited at all amyloid deposits and sites of Congophilia but not at amyloid-free sites within the tissues evaluated. Furthermore, biodistribution studies revealed that the amount of 125I deposited in liver and spleen correlated with the amount of CR birefringence (expressed as 0-4+ or as tissue area [µm2]) in these tissues with correlation coefficients of r > 0.7 (p < 10(-6)). Deposition of 125I-p5 is a quantitative measure of the amount of AA amyloid in liver and spleen in this mouse model. The p5 peptide has potential as a quantitative amyloid imaging agent in human disease.

摘要

通过非侵入性分子成像对周围淀粉样沉积物进行定量可以有助于诊断、预后判断和监测治疗反应。为了获得可靠的定量数据,有必要显示分子探针摄取与组织淀粉样负荷之间的线性正相关。使用转基因 H-2/IL-6 淀粉样变性小鼠模型产生具有不同内脏淀粉样病变阶段的动物。在注射后 2 小时,用刚果红 (CR) 染色、放射性同位素生物分布和微自动放射性照相术 (ARG) 分析注射了 125I 标记肽 p5 的组织。微 ARG 证实 125I-p5 沉积在所有淀粉样沉积物和刚果红嗜性部位,但不在评估组织中的无淀粉样部位。此外,生物分布研究表明,在肝脏和脾脏中沉积的 125I 量与这些组织中 CR 双折射的量(表示为 0-4+或组织面积 [µm2])相关,相关系数 r>0.7(p<10(-6))。在这种小鼠模型中,125I-p5 的沉积是肝和脾中 AA 淀粉样蛋白含量的定量测量。p5 肽有可能成为人类疾病的定量淀粉样成像剂。

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