Anti-angiogenic and anti-lymphangiogenic gene therapy is a new potential method for the treatment of epithelial \r\novarian carcinoma. We studied the usefulness and feasibility of diffusion-weighted magnetic resonance imaging \r\n(DW-MRI) and relaxation measurements as surrogate markers of AdsVEGFR-2, AdsVEGFR-3, AdsNRP-1 and \r\nAdsNRP-2 gene therapy treatment responses in an intraperitoneal ovarian cancer mouse model (n= 40). Gene \r\ntherapy was also combined with paclitaxel and carboplatin chemotherapy. Gene therapy was performed when visible \r\ntumors were noticed in MRI. Adenoviral gene transfer was dosed intravenously (2Ã?â??109 pfu), while chemotherapy \r\nwas dosed intraperitoneally. The study groups were: AdLacZ as controls (group I); AdsVEGFR-2 and AdsVEGFR-3 \r\n(group II); combination of AdsVEGFR-2, AdsVEGFR-3 and chemotherapy (group III) and AdsNRP-1 and AdsNRP-2 \r\n(group IV). Antitumor effectiveness was assessed by sequential MRI, immunohistochemistry, microvessel density, \r\noverall tumor growth, formation of ascites and survival time. Early responses in tumor tissue were evaluated with \r\nMRI measurements using relaxation times T2\r\n, T1?, TRAFF2, TRAFF4 and water apparent diffusion coefficient (ADC). The \r\nmean survival of mice (30 days) was significantly prolonged in group II as compared to controls (24 days) or other \r\ntreatment groups (p= 0.003). Microvessel density (MVD) and total vascular area (TVA) were significantly lower \r\ncompared to controls in all groups: group II (p= 0.001), group III (p= 0.002), group IV (p= 0.026). T2\r\n relaxation times \r\nwere significantly increased at day 8 after the gene transfer in the combination gene therapy and chemotherapy \r\ngroup III compared to controls (p= 0.005). ADC values in the tumors were significantly increased in group IV at four \r\ndays compared to controls (p= 0.044). Early changes in T2\r\n relaxation times and ADC values after gene therapy \r\nsuggest the potential of T2\r\n relaxation time measurements and DW-MRI as early markers of treatment response after \r\nanti-angiogenic gene therapy and chemotherapy.
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