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针对自身免疫性心肌炎的血管黏附蛋白-1 靶向 PET 成像。

Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis.

机构信息

Turku PET Centre, University of Turku, Åbo Akademi University and Turku University Hospital, 20520, Turku, Finland.

InFLAMES Research Flagship Center, University of Turku, Turku, Finland.

出版信息

J Nucl Cardiol. 2023 Dec;30(6):2760-2772. doi: 10.1007/s12350-023-03371-8. Epub 2023 Sep 27.

Abstract

BACKGROUND

Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis.

METHODS

Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied.

RESULTS

[Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis.

CONCLUSION

VAP-1-targeted [Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.

摘要

背景

血管黏附蛋白-1(VAP-1)是一种黏附分子和主要胺氧化酶,而镓-68 标记的 1,4,7,10-四氮杂环十二烷-N,N',N″,N‴-四乙酸连接唾液酸结合免疫球蛋白样凝集素 9 基序肽([Ga]Ga-DOTA-Siglec-9)是一种针对 VAP-1 的正电子发射断层扫描(PET)示踪剂。我们评估了使用 [Ga]Ga-DOTA-Siglec-9 进行 PET 成像以检测自身免疫性心肌炎大鼠心肌病变的可行性。

方法

将大鼠(n = 9)用完全弗氏佐剂中的猪心肌肌球蛋白免疫两次。对照组大鼠(n = 6)单独注射弗氏佐剂。在第 21 天,进行 [Ga]Ga-DOTA-Siglec-9 的体内 PET/计算机断层扫描(CT)成像,随后进行组织切片的体外放射自显影、组织学和免疫组织化学检查。此外,还研究了 3 例心脏结节病患者的心肌样本。

结果

免疫大鼠的 [Ga]Ga-DOTA-Siglec-9 PET/CT 图像显示,心肌病变部位的摄取高于病变外心肌(SUV,0.5 ± 0.1 比 0.3 ± 0.1;P =.003)或对照组大鼠(SUV,0.2 ± 0.03;P <.0001),这通过组织切片的体外放射自显影得到证实。免疫组织化学显示,心肌炎大鼠的病变部位和心脏结节病患者均存在 VAP-1 阳性染色。

结论

VAP-1 靶向的 [Ga]Ga-DOTA-Siglec-9 PET 是一种检测心肌病变的潜在新技术。

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