Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model
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Feng-Yi Yang1,2, Wen-Yuan Chang1, Wei-Ting Lin1, Jeng-Jong Hwang1, Yi-Chun Chien1, Hsin-Ell Wang1, Min-Lan Tsai3
1Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
2Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan
3Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan
Feng-Yi Yang, e-mail: [email protected]
Jeng-Jong Hwang, e-mail: [email protected]
Keywords: focused ultrasound, molecular imaging, gene therapy, blood-brain barrier, brain tumor
Received: July 11, 2015 Accepted: September 14, 2015 Published: September 25, 2015
The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2’-fluoro-2’-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P < 0.05) of glioma cells on day 16 after implantation. Moreover, combining sonication with GCV significantly inhibited tumor growth compared with GCV alone. This study demonstrated that FUS may be used to deliver a wide variety of theranostic agents to the brain for molecular imaging and gene therapy in brain diseases.
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