Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR EJNMMI Radiopharmacy and Chemistry Pub Date : 2023-09-21 DOI:10.1186/s41181-023-00210-6

Olivia Wegrzyniak, Bo Zhang, Johanna Rokka, Maria Rosestedt, Bogdan Mitran, Pierre Cheung, Emmi Puuvuori, Sofie Ingvast, Jonas Persson, Helena Nordström, John Löfblom, Fredrik Pontén, Fredrik Y. Frejd, Olle Korsgren, Jonas Eriksson, Olof Eriksson

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引用次数: 1

Abstract

Background

Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([¹⁸F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis.

Results

In vitro specificity studies demonstrated that the trans-Cyclooctenes (TCO) conjugated Z09591 Affibody molecule had a picomolar affinity for human PDGFRβ. Biodistribution performed on healthy rats showed rapid clearance of [¹⁸F]TZ-Z09591 through the kidneys and low liver background uptake. Autoradiography (ARG) studies on fibrotic livers from mice or humans correlated with histopathology results. Ex vivo biodistribution and ARG revealed that [¹⁸F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars.

Conclusions

Our study highlights [18F]TZ-Z09591 as a specific tracer for fibrogenic cells in the fibrotic liver, thus offering the potential to assess fibrogenesis clearly.

Graphical abstract

Abstract Image

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[18F]TZ-Z09591（一种靶向血小板衍生生长因子受体β的亲和分子）对肝脏纤维化的成像。

背景：血小板衍生生长因子受体β（PDGFRβ）是一种在活化的肝星状细胞（aHSC）上过表达的受体。PDGFRβ的正电子发射断层扫描（PET）成像有可能量化纤维化肝脏的纤维化发生。本研究旨在评估一种氟-18放射性标记的亲和体分子（[18F]TZ-Z09591）作为肝脏纤维化成像的PET示踪剂。结果：体外特异性研究表明，反式-环辛烯（TCO）偶联的Z09591亲和体分子对人PDGFRβ具有皮摩尔亲和力。在健康大鼠身上进行的生物分布显示[18F]TZ-Z09591通过肾脏的快速清除和低肝脏背景摄取。小鼠或人类纤维化肝脏的自动放射线照相（ARG）研究与组织病理学结果相关。离体生物分布和ARG显示[18F]TZ-Z09591在纤维化肝脏中的结合增加（p = 0.02），并且对应于纤维化瘢痕中的结合。结论：我们的研究强调[18F]TZ-Z09591是纤维化肝脏中纤维化细胞的特异性示踪剂，从而提供了明确评估纤维化发生的潜力。

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