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.
J Nucl Cardiol. 2023 Dec;30(6):2760-2772. doi: 10.1007/s12350-023-03371-8. Epub 2023 Sep 27.
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.
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.
[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.
VAP-1-targeted [Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.
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。
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。
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。
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。