Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir

Win Ping Deng, Cheng Chia Wu, Chien Chih Lee, Wen K. Yang, Hsin Ell Wang, Ren Shyan Liu, Hon Jian Wei, Juri G. Gelovani, Jeng Jong Hwang, Den Mei Yang, Ying Kai Fu, Cheng Wen Wu

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Noninvasive imaging in lung metastatic tumor models is used infrequently because of technical limitations in detecting metastases. We have previously used 2′-fluoro-2′-deoxy-5-iodo-1-β-D-arabinofuranosyluracil labeled with 131I (131I-FIAU) and demonstrated the applicability of noninvasive imaging for monitoring cancer gene therapy in an experimental animal model of herpes simplex virus type 1 thymidine kinase (HSV1-tk)-expressing tumor xenografts.We have now used the same animal model to effectively and noninvasively monitor the location, magnitude, and duration of therapeutic gene expression over time for the lung metastases model. Methods: To improve the detectability of lung metastases, an experimental blood-borne lung metastases model in mice was established using intravenously administered HSV1-tk-expressing NG4TL4 fibrosarcoma cells (NG4TL4-TK) and simulated the clinical application of HSV1-tk plus ganciclovir (GCV) prodrug activation gene therapy. The efficacy of noninvasively monitoring the sites of development of lung metastatic lesions and their GCV-induced regression were assessed by SPECT with 131I-FIAU. Results: The results of this study showed that the lung metastases model of NG4TL4-TK cells could be successfully detected as early as 24 h after intravenous injection of tumor cells radiolabeled with 131I-FIAU and also subsequently detected by extended monitoring with the intravenous injection of 131I-FIAU on day 10. In mice treated with GCV, γ-camera imaging demonstrated a significant growth inhibition of NG4TL4-TK cells of primary tumors and lung metastases on day 7 after initiating treatment. Conclusion: We conclude that this in vivo imaging approach will be useful for future studies of the lung metastases model and for the assessment of novel anti-cancer and antimetastatic therapies.

Original languageEnglish
Pages (from-to)877-884
Number of pages8
JournalJournal of Nuclear Medicine
Volume47
Issue number5
Publication statusPublished - May 1 2006

Keywords

  • I-FIAU
  • Ganciclovir
  • Gene therapy
  • Herpes simplex virus thymidine kinase
  • Lung metastases model
  • Noninvasive imaging
  • Reporter gene

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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