Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir.
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-beta-d-arabinofuranosyluracil labeled with (131)I ((131)I-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 (131)I-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 (131)I-FIAU and also subsequently detected by extended monitoring with the intravenous injection of (131)I-FIAU on day 10. In mice treated with GCV, gamma-camera imaging demonstrated a significant growth inhibition of NG4TL4-TK cells of primary tumors and lung metastases on day 7 after initiating treatment.


CONCLUSIONS
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 anticancer and antimetastatic therapies.
Deng
Win-Ping
WP
Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan. wpdeng@ms41.hinet.net
Wu
Cheng-Chia
CC
Lee
Chien-Chih
CC
Yang
Wen K
WK
Wang
Hsin-Ell
HE
Liu
Ren-Shyan
RS
Wei
Hon-Jian
HJ
Gelovani
Juri G
JG
Hwang
Jeng-Jong
JJ
Yang
Den-Mei
DM
Fu
Ying-Kai
YK
Wu
Cheng-Wen
CW
D000818:Animals; D015774:Ganciclovir / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D018259:Herpesvirus 1, Human / Q000235:genetics; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D051379:Mice; D009362:Neoplasm Metastasis; D011877:Radionuclide Imaging; D013937:Thymidine Kinase / Q000235:genetics; D014018:Tissue Distribution
D013937:Thymidine Kinase; D015774:Ganciclovir