Evaluation of ¹⁷⁷Lu-Labeled Lipiodol as a Targeted Radionuclide Therapy for Hepatocellular Carcinoma in a Preclinical Xenograft Model.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-06-04 DOI:10.1007/s11307-025-02016-1

Yumiko Kono, Keita Utsunomiya, Takahiro Shiraishi, Naoki Kan, Ichiro Shiojima, Kaoru Maruyama, Noboru Tanigawa

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引用次数: 0

Abstract

Background: Lutetium-177 (¹⁷⁷Lu) is a promising radionuclide for targeted cancer therapy due to its favorable theranostic properties. Transarterial lipiodol embolization is widely used for hepatocellular carcinoma (HCC), but the potential of ¹⁷⁷Lu emulsified into lipiodol (¹⁷⁷Lu-lipiodol) remains underexplored. This study aimed to evaluate the partition coefficient, biodistribution, and antitumor efficacy of ¹⁷⁷Lu-lipiodol in a preclinical xenograft model.

Methods: After synthesizing ¹⁷⁷Lu-oxine from ¹⁷⁷Lu-chloride, the product was emulsified in lipiodol. Its radiochemical purity and partition coefficient were measured. F344 NJcl rnu/nu rats (n = 5) bearing bilateral thigh tumors (HC-4 cells) were randomized to receive ¹⁷⁷Lu-lipiodol (2.8 MBq in 50 μL) or non-labeled lipiodol (50 μL) via surgical exposure and direct puncture of the right femoral artery. SPECT/CT images were acquired over 14 days, and biodistribution was confirmed by gamma counting at day 28. Tumor volumes and body weights were monitored to assess treatment response and toxicity.

Results: The ¹⁷⁷Lu-lipiodol emulsion was obtained with a high radiochemical purity (> 99%). SPECT/CT showed high tumor accumulation (34.0% ± 4.4% immediately post-injection) that persisted up to day 28 (7.3% ± 1.2% of injected dose). Tumor growth was significantly suppressed with a treated-to-untreated volume ratio of 0.45 at day 14 (p = 0.017) and 0.59 at day 21 (p = 0.001). While off-target uptake was limited, moderate splenic accumulation (26.6% ± 17.5% ID) was noted. No marked body weight changes or gross organ abnormalities were observed.

Conclusion: ¹⁷⁷Lu-lipiodol for HCC therapy demonstrated effective tumor targeting and growth suppression of HCC in a preclinical xenograft model.

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177lu标记的脂醇作为靶向放射性核素治疗肝细胞癌的临床前异种移植模型的评估。

背景：镥-177 （177Lu）由于其良好的治疗特性，是一种很有前途的靶向癌症治疗放射性核素。经动脉脂醇栓塞广泛用于肝细胞癌（HCC），但177Lu乳化成脂醇（177Lu-lipiodol）的潜力仍未得到充分探索。本研究旨在评价177lu -脂醇在临床前异种移植模型中的分配系数、生物分布和抗肿瘤功效。方法：以氯化177lu为原料合成177Lu-oxine，用脂醇乳化。测定了其放射化学纯度和分配系数。选择携带双侧大腿肿瘤（HC-4细胞）的F344只NJcl rnu/nu大鼠（n = 5），通过手术暴露和直接穿刺右股动脉，随机给予177Lu-lipiodol （2.8 MBq, 50 μL）或非标记lipiodol （50 μL）。在14天内获得SPECT/CT图像，并在28天通过伽马计数确认生物分布。监测肿瘤体积和体重以评估治疗反应和毒性。结果：制备的177lu -脂醇乳状液具有较高的放射化学纯度（约99%）。SPECT/CT显示高肿瘤积聚（注射后立即为34.0%±4.4%），持续至第28天（注射剂量的7.3%±1.2%）。肿瘤生长明显受到抑制，第14天治疗与未治疗的体积比为0.45 (p = 0.017)，第21天为0.59 （p = 0.001）。虽然脱靶摄取有限，但注意到中度脾积聚（26.6%±17.5% ID）。未观察到明显的体重变化或脏器异常。结论：177lu - lipodol用于HCC治疗在临床前异种移植模型中显示出有效的肿瘤靶向和肝癌生长抑制作用。

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

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.