Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model

// Feng-Yi Yang 1, 2 , Wen-Yuan Chang 1 , Wei-Ting Lin 1 , Jeng-Jong Hwang 1 , Yi-Chun Chien 1 , Hsin-Ell Wang 1 , Min-Lan Tsai 3 1 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan 2 Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan 3 Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan Correspondence to: Feng-Yi Yang, e-mail: fyyang@ym.edu.tw Jeng-Jong Hwang, e-mail: jjhwang@ym.edu.tw Keywords: focused ultrasound, molecular imaging, gene therapy, blood-brain barrier, brain tumor Received: July 11, 2015      Accepted: September 14, 2015      Published: September 25, 2015 ABSTRACT 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 123 I-2’-fluoro-2’-deoxy-5-iodo-1-β-D-arabinofuranosyluracil ( 123 I-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 123 I-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.