Zhang Xiaoli, Li Tingting, Tong Jindong, Zhou Meihong, Wang Zi, Liu Xingdang, Lu Wei, Lou Jingjing, Yi Qingtong
Department of Urology and Department of Nuclear Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.
Quzhou Fudan Institute, Quzhou 324002, China.
Pharmaceutics. 2024 Dec 17;16(12):1609. doi: 10.3390/pharmaceutics16121609.
BACKGROUND/OBJECTIVES: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (F-FDG PET/CT).
DEBs were prepared by polyvinyl alcohol-based macromer crosslinked with -acryl tyrosine and ,'-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs. Their particle size and drug release profile were characterized. VX2 tumors were implanted in the right kidney of rabbits to establish the renal tumor model. The tumor-bearing rabbits received pre-scan by F-FDG PET/CT, followed by targeted transarterial injection of G-DEBs under digital subtraction angiography (DSA) guidance. The rabbits received another F-FDG PET/CT scan 10 or 14 days after the treatment. The therapeutic effect was further validated by histopathological analysis of the dissected tumors.
The average particle size of the microspheres was 58.06 ± 0.50 µm, and the polydisperse index was 0.26 ± 0.002. The maximum loading rate of G-DEBs was 18.09 ± 0.35%, with almost 100% encapsulation efficiency. Within 24 h, GEM was eluted from G-DEBs rapidly and completely, and more than 20% was released in different media. DSA illustrated that G-DEBs were delivered to rabbit renal tumors. Compared with the untreated control group with increased tumor volume and intense F -FDG uptake, the G-DEBs group showed significant reductions in tumor volume and maximum standard uptake value (SUV) 10 or 14 days after the treatment. Histopathological analysis confirmed that the proliferating area of tumor cells was significantly reduced in the G-DEBs group.
Our results demonstrated that G-DEBs are effective in TACE treatment of rabbit VX2 renal tumors, and F-FDG PET/CT provides a non-invasive imaging modality to monitor the antitumor effects of TACE in renal tumors.
背景/目的：本研究旨在研发用于兔肾肿瘤经动脉化疗栓塞术（TACE）的载吉西他滨药物洗脱微球（G-DEBs），并使用2-脱氧-2-[(18)F]氟-D-葡萄糖正电子发射断层扫描/X射线计算机断层扫描（F-FDG PET/CT）评估其抗肿瘤效果。
通过聚乙烯醇基大分子单体与α-丙烯酰酪氨酸和N,N'-亚甲基双丙烯酰胺交联制备微球。通过离子交换加载吉西他滨以获得G-DEBs。对其粒径和药物释放曲线进行表征。将VX2肿瘤植入兔右肾以建立肾肿瘤模型。荷瘤兔先接受F-FDG PET/CT预扫描，然后在数字减影血管造影（DSA）引导下经动脉靶向注射G-DEBs。治疗后10或14天，兔再次接受F-FDG PET/CT扫描。通过对切除肿瘤的组织病理学分析进一步验证治疗效果。
微球的平均粒径为58.06±0.50 µm，多分散指数为0.26±0.002。G-DEBs的最大载药率为18.09±0.35%，包封率几乎为100%。在24小时内，GEM从G-DEBs中快速且完全洗脱，在不同介质中释放超过20%。DSA显示G-DEBs被输送至兔肾肿瘤。与肿瘤体积增大且F-FDG摄取强烈的未治疗对照组相比，G-DEBs组在治疗后10或14天肿瘤体积和最大标准摄取值（SUV）显著降低。组织病理学分析证实G-DEBs组肿瘤细胞增殖区域显著减少。
我们的结果表明G-DEBs在兔VX2肾肿瘤的TACE治疗中有效，且F-FDG PET/CT提供了一种非侵入性成像方式来监测TACE对肾肿瘤的抗肿瘤效果。
