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 journalArticle

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

Fingerprint

Ganciclovir
Thymidine Kinase
Human Herpesvirus 1
Genetic Therapy
Neoplasm Metastasis
Lung
Neoplasms
Intravenous Injections
Arabinofuranosyluracil
Animal Models
Fibrosarcoma
Neoplasm Genes
Prodrugs
Single-Photon Emission-Computed Tomography
Heterografts
Therapeutics
Gene Expression
fialuridine
Growth

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

Cite this

Deng, W. P., Wu, C. C., Lee, C. C., Yang, W. K., Wang, H. E., Liu, R. S., ... Wu, C. W. (2006). Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir. Journal of Nuclear Medicine, 47(5), 877-884.

Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir. / Deng, Win Ping; Wu, Cheng Chia; Lee, Chien Chih; Yang, Wen K.; Wang, Hsin Ell; Liu, Ren Shyan; Wei, Hon Jian; Gelovani, Juri G.; Hwang, Jeng Jong; Yang, Den Mei; Fu, Ying Kai; Wu, Cheng Wen.

In: Journal of Nuclear Medicine, Vol. 47, No. 5, 01.05.2006, p. 877-884.

Research output: Contribution to journalArticle

Deng, WP, Wu, CC, Lee, CC, Yang, WK, Wang, HE, Liu, RS, Wei, HJ, Gelovani, JG, Hwang, JJ, Yang, DM, Fu, YK & Wu, CW 2006, 'Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir', Journal of Nuclear Medicine, vol. 47, no. 5, pp. 877-884.
Deng, Win Ping ; Wu, Cheng Chia ; Lee, Chien Chih ; Yang, Wen K. ; Wang, Hsin Ell ; Liu, Ren Shyan ; Wei, Hon Jian ; Gelovani, Juri G. ; Hwang, Jeng Jong ; Yang, Den Mei ; Fu, Ying Kai ; Wu, Cheng Wen. / Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir. In: Journal of Nuclear Medicine. 2006 ; Vol. 47, No. 5. pp. 877-884.
@article{380818aeb38f4723b61a4ab6dd04e02c,
title = "Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir",
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.",
keywords = "I-FIAU, Ganciclovir, Gene therapy, Herpes simplex virus thymidine kinase, Lung metastases model, Noninvasive imaging, Reporter gene",
author = "Deng, {Win Ping} and Wu, {Cheng Chia} and Lee, {Chien Chih} and Yang, {Wen K.} and Wang, {Hsin Ell} and Liu, {Ren Shyan} and Wei, {Hon Jian} and Gelovani, {Juri G.} and Hwang, {Jeng Jong} and Yang, {Den Mei} and Fu, {Ying Kai} and Wu, {Cheng Wen}",
year = "2006",
month = "5",
day = "1",
language = "English",
volume = "47",
pages = "877--884",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "5",

}

TY - JOUR

T1 - Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir

AU - Deng, Win Ping

AU - Wu, Cheng Chia

AU - Lee, Chien Chih

AU - Yang, Wen K.

AU - Wang, Hsin Ell

AU - Liu, Ren Shyan

AU - Wei, Hon Jian

AU - Gelovani, Juri G.

AU - Hwang, Jeng Jong

AU - Yang, Den Mei

AU - Fu, Ying Kai

AU - Wu, Cheng Wen

PY - 2006/5/1

Y1 - 2006/5/1

N2 - 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.

AB - 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.

KW - I-FIAU

KW - Ganciclovir

KW - Gene therapy

KW - Herpes simplex virus thymidine kinase

KW - Lung metastases model

KW - Noninvasive imaging

KW - Reporter gene

UR - http://www.scopus.com/inward/record.url?scp=33745552227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745552227&partnerID=8YFLogxK

M3 - Article

C2 - 16644759

AN - SCOPUS:33745552227

VL - 47

SP - 877

EP - 884

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 5

ER -