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Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents

  • Hao Wu
  • Zhi-Pu Fan
  • An-Na Jiang
  • Xing-Sheng Di
  • Bing He
  • Song Wang
  • S. Nahum Goldberg
  • Muneeb Ahmed
  • Qiang Zhang
  • Wei YangEmail author
Oncology
  • 21 Downloads

Abstract

Objectives

To determine whether radiofrequency ablation (RFA) is more effective when combined with intratumoural injection (IT) than with intravenous injection (IV) of micelles.

Materials and methods

Balb/c mice bearing 4T1 breast cancer were used. The tumour drug accumulation and biodistribution in major organs were evaluated at different time points after IT, IV, IT+RFA and IV+RFA. Periablational drug penetration was evaluated by quantitative analysis and pathologic staining after different treatments. For long-term outcomes, mice bearing tumours were randomised into six groups (n = 7/group): the control, IV, IT, RFA alone, IV+RFA and IT+RFA groups. The end-point survival was estimated for the different treatment groups.

Results

In vivo, intratumoural drug accumulation was always much higher for IT than for IV within 48 h (p < 0.001). The IT+RFA group (3084.7 ± 985.5 μm) exhibited greater and deeper drug penetration than the IV+RFA group (686.3 ± 83.7 μm, p < 0.001). Quantitatively, the intratumoural drug accumulation in the IT+RFA group increased approximately 4.0-fold compared with that in the IV+RFA group (p < 0.001). In addition, compared with the IT treatment, the IT+RFA treatment further reduced the drug deposition in the main organs. Survival was longer in the IT+RFA group than in the IV+RFA (p = 0.033) and RF alone (p = 0.003) groups.

Conclusion

The use of IT+RFA achieved much deeper and greater intratumoural drug penetration and accumulation, resulting in better efficacy, and decreased the systemic toxicity of nanoparticle-delivered chemotherapy.

Key Points

• Association of IT+RFA achieved much deeper and greater intratumoural drug penetration than of IV+RFA, leading to better therapeutic efficacy.

• Compared with IV or IT chemotherapy alone, the combination with RFA decreased toxicity, especially in the IT+RFA group.

Keywords

Mice, inbred Babl/c Micelles Injections, intravenous Injections, intralesional Radiofrequency ablation 

Abbreviations

RFA

Radiofrequency ablation

IT

Intratumoural injection

IV

Intravenous injection

PTX

Paclitaxel

Notes

Funding

This study has received funding by the National Natural Science Foundation of China (Grant Nos. 81471768, 81773286, 81571674 and 81771853).

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Yang Wei.

Conflict of interest

One author (S.N.G.) receives consulting fees from Angiodynamics and Cosman Company. These companies had no control or involvement in data collection, data analysis, or manuscript preparation. Other authors had no conflict of interest and had unrestricted control of study data.

Statistics and biometry

Goldberg SN, Ahmed Muneeb and Zhang Qiang kindly provided statistical and constructive advice for this manuscript.

Informed consent

Approval from the institutional animal care committee was obtained.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Experimental

• Performed at one institution

Supplementary material

330_2019_6207_MOESM1_ESM.docx (4.8 mb)
ESM 1 (DOCX 4961 kb)

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Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Hao Wu
    • 1
    • 2
  • Zhi-Pu Fan
    • 3
  • An-Na Jiang
    • 1
  • Xing-Sheng Di
    • 3
  • Bing He
    • 3
  • Song Wang
    • 1
  • S. Nahum Goldberg
    • 4
    • 5
  • Muneeb Ahmed
    • 4
  • Qiang Zhang
    • 3
  • Wei Yang
    • 1
    Email author
  1. 1.Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education /Beijing)Peking University Cancer Hospital & InstituteBeijingChina
  2. 2.Department of UltrasonographyGuangdong Second Provincial General Hospital Affiliated to Southern Medical UniversityGuangzhouChina
  3. 3.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  4. 4.Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  5. 5.Division of Image-Guided Therapy, Department of RadiologyHadassah Hebrew University Medical CenterJerusalemIsrael

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