Martin Emily B, Williams Angela, Richey Tina, Stuckey Alan, Heidel R Eric, Kennel Stephen J, Wall Jonathan S
Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
Department of Radiology, and University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
Sci Rep. 2016 Mar 3;6:22695. doi: 10.1038/srep22695.
Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US.
淀粉样变性是一种蛋白质错误折叠疾病，其特征是淀粉样蛋白在细胞外沉积，淀粉样蛋白是一种由蛋白质原纤维、高硫酸化糖胺聚糖和血清淀粉样蛋白P成分（SAP）组成的复杂基质。淀粉样蛋白在内脏器官中的积累导致组织结构破坏，进而导致器官功能障碍和衰竭。早期鉴别诊断和疾病监测对于改善患者预后至关重要；因此，全身淀粉样蛋白成像在这方面将是有益的。在欧洲，通过使用碘-123标记的SAP对系统性淀粉样蛋白进行非侵入性分子成像；然而，这种示踪剂在美国无法获得。因此，我们评估了合成的多碱性肽，命名为p5和p5+14，作为检测系统性淀粉样变性的替代放射性示踪剂。在此，我们使用双能SPECT成像和组织生物分布测量，对载有淀粉样蛋白的小鼠体内放射性标记的肽p5+14与p5和SAP进行了比较有效性评估。所有三种放射性示踪剂在体内均能选择性地结合淀粉样蛋白；然而，在某些器官中，p5+14比p5显著更有效。此外，SAP主要结合肝脾淀粉样蛋白，而p5+14广泛分布于许多载有淀粉样蛋白的解剖部位，包括脾脏、肝脏、胰腺、肠道和心脏。这些数据支持将p5+14作为美国患者的淀粉样蛋白放射性示踪剂进行临床验证。
