title: Focused ultrasound enhanced molecular imaging and gene therapy for multifusion reporter gene in glioma-bearing rat model.
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 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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.|Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Chang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Lin
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chien
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Min-Lan
authors.initials: ML
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000032:analysis; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D007457:Iodine Radioisotopes / Q000032:analysis; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D019275:Radiopharmaceuticals / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014463:Ultrasonography / Q000379:methods
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil
keywords: blood-brain barrier; brain tumor; focused ultrasound; gene therapy; molecular imaging