Kono Yumiko, Utsunomiya Keita, Shiraishi Takahiro, Kan Naoki, Shiojima Ichiro, Maruyama Kaoru, Tanigawa Noboru
Department of Radiology, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan.
Radioisotope Research Center, Kansai Medical University, 2-5-1 Shin-Machi, Hirakata City, Osaka, 573-1010, Japan.
Mol Imaging Biol. 2025 Jun 4. doi: 10.1007/s11307-025-02016-1.
Lutetium-177 (Lu) 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 Lu emulsified into lipiodol (Lu-lipiodol) remains underexplored. This study aimed to evaluate the partition coefficient, biodistribution, and antitumor efficacy of Lu-lipiodol in a preclinical xenograft model.
After synthesizing Lu-oxine from Lu-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 Lu-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.
The Lu-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.
Lu-lipiodol for HCC therapy demonstrated effective tumor targeting and growth suppression of HCC in a preclinical xenograft model.
镥-177（Lu）因其良好的诊疗特性，是一种很有前景的用于靶向癌症治疗的放射性核素。经动脉碘油栓塞术广泛应用于肝细胞癌（HCC），但乳化于碘油中的镥（Lu-碘油）的潜力仍未得到充分探索。本研究旨在评估Lu-碘油在临床前异种移植模型中的分配系数、生物分布及抗肿瘤疗效。
由氯化镥合成氧代镥后，将产物乳化于碘油中。测定其放射化学纯度和分配系数。将双侧大腿有肿瘤（HC-4细胞）的F344 NJcl rnu/nu大鼠（n = 5）随机分组，通过手术暴露并直接穿刺右股动脉，分别接受Lu-碘油（50 μL中含2.8 MBq）或未标记碘油（50 μL）。在14天内采集SPECT/CT图像，并在第28天通过γ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。
获得了放射化学纯度高（>99%）的Lu-碘油乳剂。SPECT/CT显示肿瘤摄取率高（注射后立即为34.0%±4.4%），直至第28天仍持续存在（注射剂量的7.3%±1.2%）。在第14天，肿瘤生长受到显著抑制，治疗组与未治疗组的体积比为0.45（p = 0.017），在第21天为0.59（p = 0.001）。虽然非靶器官摄取有限，但观察到脾脏有中度摄取（26.6%±17.5% ID）。未观察到明显的体重变化或大体器官异常。
在临床前异种移植模型中，用于HCC治疗的Lu-碘油显示出对HCC有效的肿瘤靶向性和生长抑制作用。
