PET imaging of hepatocellular carcinoma with [¹²⁴I]IV-14.

IF 3.1 3区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

EJNMMI Research Pub Date : 2025-04-07 DOI:10.1186/s13550-025-01227-5

Wei Cao, Olga Sergeeva, William Julian, Adam Kresak, Destiny Lusinger, Joseph Schneider, Marc S Berridge, Sandra Sexton, Patrick Wojtylak, Qiubai Li, Wendy Liu, Ernest Ricky Chan, Yogen Saunthararajah, Zhenghong Lee

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引用次数: 0

Abstract

Background: Currently, positron emission tomography (PET) plays no clear role in clinical imaging and management of hepatocellular carcinoma (HCC). New radiotracers for new target(s) are needed for PET imaging of HCC. Uridine-cytidine kinase 2 (UCK2) is a rate-limiting enzyme of the pyrimidine salvage synthesis pathway to phosphorylate uridine and cytidine. Studies have demonstrated that UCK2 is overexpressed in many types of solid cancers including HCC and is associated with the poor prognosis and proliferation of HCC. This study reported PET imaging using a UCK2-specific radiotracer with a clinically relevant anima model of spontaneously occurring HCC in the woodchucks.

Methods: This study used 3'-(E)-(2-iodovinyl) uridine (IV-14), which is derived from a UCK2-selective antitumor agent 3'-(Ethynyl)uridine (EUrd), a cytotoxic ribonucleoside analogs of uridine. By radiolabeling IV-14 with Iodine-124 (¹²⁴I), a UCK2-specific radiotracer [¹²⁴I]IV-14 was obtained for PET imaging of UCK2. A naturally occurring woodchuck model of HCC following chronic viral hepatitis infection was used for PET imaging. Potassium iodide (KI) was tested in one of the three animals to block possible uptake of free ¹²⁴I from de-iodination of [¹²⁴I]IV-14.

Results: We confirmed that UCK2 expression is higher in the woodchuck model of HCC than in the surrounding hepatic tissue, similar to human UCK2 that is highly expressed in human HCC. PET imaging with [¹²⁴I]IV-14 showed a strong uptake in woodchuck HCC with low background uptake at one-hour post-injection. De-iodination did not seem to be an issue for PET imaging.

Conclusion: Our results demonstrate that UCK2 is a viable target for imaging HCC and has the potential for targeted endoradiotherapy of HCC.

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[124I]IV-14肝细胞癌的PET显像。

背景：目前，正电子发射断层扫描（PET）在肝细胞癌（HCC）的临床成像和治疗中没有明确的作用。肝癌的PET显像需要新的靶向示踪剂。尿苷-胞苷激酶2 （UCK2）是嘧啶回收合成途径的限速酶，可使尿苷和胞苷磷酸化。研究表明，UCK2在包括HCC在内的多种实体癌中过表达，并与HCC预后不良和增殖有关。本研究报道了使用uck2特异性放射性示踪剂的PET成像与土拔鼠自发发生的HCC的临床相关动物模型。方法：本研究使用了3'-(E)-（2-碘乙烯基）尿苷（IV-14），它是从uck2选择性抗肿瘤药物3'-（乙基）尿苷（EUrd）中衍生出来的，EUrd是一种具有细胞毒性的尿苷类似物。用碘-124 （124I）对IV-14进行放射性标记，获得UCK2特异性放射性示踪剂[124I]IV-14，用于UCK2的PET成像。采用自然发生的慢性病毒性肝炎后肝细胞癌土拨鼠模型进行PET成像。碘化钾（KI）在三只动物中的一只身上进行了测试，以阻止从[124I]IV-14去碘中可能摄取游离124I。结果：我们证实UCK2在土拨鼠肝细胞癌模型中的表达高于肝周围组织，与人UCK2在人肝细胞癌中的高表达相似。[124I]IV-14 PET成像显示注射后1小时土拨鼠肝细胞癌摄取强，背景摄取低。去碘似乎不是PET成像的问题。结论：我们的研究结果表明，UCK2是HCC成像的可行靶点，具有靶向肝癌放射治疗的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EJNMMI Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-

CiteScore

5.90

自引率

3.10%

发文量

审稿时长

13 weeks

期刊介绍： EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies. The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.