期刊
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
卷 45, 期 12, 页码 1834-1841出版社
SPRINGER
DOI: 10.1007/s00270-022-03242-8
关键词
Transcatheter arterial chemoembolization; Hepatocellular carcinoma; Lenvatinib; Drug eluting microspheres; Local drug delivery
资金
- National Cancer Institute [R01CA218659, R01EB026207]
- National Institute of Biomedical Imaging and Bioengineering
- Center for Translational Imaging and Mouse Histology and Phenotyping Laboratory at Northwestern University
This study evaluated the therapeutic response of Lenvatinib-eluting microspheres (LEN-EM) transcatheter arterial chemoembolization (LEN-TACE) in an hepatocellular carcinoma (HCC) rat model. LEN-EM with good loading efficiency and controlled release properties was used for LEN-TACE treatment. The results showed that LEN-TACE effectively reduced tumor volume and had minimal side effects in the HCC rat model.
Purpose To evaluate the preclinical in vivo therapeutic response of Lenvatinib-eluting microspheres (LEN-EM) transcatheter arterial chemoembolization (LEN-TACE) in an hepatocellular carcinoma (HCC) rat model. Methods Magnetic resonance imaging (MRI) visible LEN-EM was fabricated with poly(lactide-co-glycolide) and iron oxide nanoparticles by a double-emulsion method. The morphology, LEN loading/release kinetics, and MRI contrast effect of LEN-EM were evaluated. For in vivo study, N1S1 HCC rats were treated with LEN-TACE (LEN: 2.4 mg/kg, n = 5) using LEN-EM, systemic LEN (LEN: 0.4 mg/kg, oral gavage daily for 7 days, n = 5), control (intra-arterial (IA) saline infusion, n = 5), and non-tumor control (n = 3). Tumor size changes were measured for 2 weeks. Histology, comparative LEN plasma concentration, hematologic markers, liver profile, and serum chemistry among the groups were measured. Results LEN-EM with 33 mu m in average size was prepared in an optimized emulsion process. LEN loading efficiency was 58.7%. LEN was continuously released for 500 h. LEN-TACE showed the delivered LEN-EM surrounding tumor tissue in MRI-T2* images. The LEN-TACE group demonstrated a statistically significant larger tumor volume reduction compared to the other groups at 2 weeks post-procedure. Quantification data of Terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells confirmed increased cancer cell death in the LEN-TACE group compared to control groups. Additional histology, hematologic markers, and liver profiles showed minimal side effects of LEN-TACE. Conclusion LEN-TACE using IA delivery of LEN-EM demonstrated an effective therapeutic efficacy in an HCC rat animal model.
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