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Monitoring Tumor Response with Radiolabeled Nucleoside Analogs in a Hepatoma-Bearing Mouse Model Early After Doxisome® Treatment

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Abstract

Purpose

This study aims to demonstrate that 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) positron emission tomography (PET) is a promising modality for noninvasively monitoring the therapeutic efficacy of Doxisome® in a subcutaneous hepatoma mouse model.

Procedures

Male BALB/c nu/nu mice were inoculated with HepG2 hepatoma xenograft in the right flank. Doxisome® (5 mg/kg, three times a week for 2 weeks) was intravenously administrated for treatment. 18F-FLT-microPET, biodistribution studies, and immunohistochemistry of Ki-67 were performed.

Results

A significant difference (p < 0.05) in tumor volume was observed on day 5 between treated and control groups. The tumor-to-muscle ratio derived from 18F-FLT-PET and 123I-ICdR-microSPECT images of Doxisome®-treated mice dropped from 12.55 ± 0.76 to 3.81 ± 0.31 and from 2.48 ± 0.42 to 1.59 ± 0.08 after a three-dose treatment, respectively, while that of the control group remained steady. The retarded proliferation rate of treated xenograft was confirmed by Ki-67 immunohistochemistry staining.

Conclusions

This study clearly demonstrated that Doxisome® is an effective anti-cancer drug against the growth of HepG2 hepatoma and that 18F-FLT-PET could provide early information of tumor response during treatment.

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Acknowledgments

The authors thank the financial support from the National Science Council, Taiwan (NSC100-2623-E-010-003-NU and NSC99-NU-E-010-003), Department of Health, Taipei City Government, Taiwan (99001-62-034), and Cheng Hsin General Hospital, Taiwan (98F117CY07). The authors also appreciate the technical support from the National Research Program for Genetic Medicine, Taiwan (Molecular and Genetic Core, NSC100-2319-B-010-003).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No.155, Sec.2, Li-Nong St., Taipei, Taiwan, 11217

    Chun-Yi Wu, Lin-Shan Chou, Pei-Chia Chan, Chung-Hsien Ho, Ren-Shyan Liu & Hsin-Ell Wang

  2. Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan

    Ming-Hsien Lin

  3. Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

    Chih-Chieh Shen

  4. Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan

    Ren-Shyan Liu

  5. Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Ren-Shyan Liu

  6. Atomic Energy Council, Institute of Nuclear Energy Research, Tao-Yuan, Taiwan

    Wuu-Jyh Lin

  7. National PET/Cyclotron Center, Taipei Veterans General Hospital, 201, Sec.2, Shih-Pai Rd., Taipei, Taiwan, 11217

    Ren-Shyan Liu

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  1. Chun-Yi Wu
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Correspondence to Ren-Shyan Liu or Hsin-Ell Wang.

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Wu, CY., Chou, LS., Chan, PC. et al. Monitoring Tumor Response with Radiolabeled Nucleoside Analogs in a Hepatoma-Bearing Mouse Model Early After Doxisome® Treatment. Mol Imaging Biol 15, 326–335 (2013). https://doi.org/10.1007/s11307-012-0604-9

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  • DOI: https://doi.org/10.1007/s11307-012-0604-9

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