alexa Functional MRI Measurements to Predict Early Adenoviral Gene Therapy Response in Ovarian Cancer Mouse Model
ISSN: 2157-7412

Journal of Genetic Syndromes & Gene Therapy
Open Access

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Research Article

Functional MRI Measurements to Predict Early Adenoviral Gene Therapy Response in Ovarian Cancer Mouse Model

Tuppurainen L1, Sallinen H1,2,3, Hakkarainen H1,4, Liimatainen T1,4, Hassan M1, Ylä-Herttuala E1,4, Anttila M1,2,3, Hämäläinen K2,5, Veli-Matti Kosma2,5, Heinonen S2,3, Alitalo K6 and Ylä-Herttuala S1,7,8*

1Department of Biotechnology and Molecular Medicine, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

2Institute of Clinical Medicine, Gynecology, and Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland

3Department of Gynecology, Kuopio University Hospital, Kuopio, Finland

4Cardiovascular Imaging Group, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

5Department of Pathology, Kuopio University Hospital, Kuopio, Finland

6Molecular/Cancer Biology Laboratory Biomedicum Helsinki and Haartman Institute, University of Helsinki, Helsinki, Finland

7Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland

8Research Unit, Kuopio University Hospital, Kuopio, Finland

*Corresponding Author:
Seppo Ylä-Herttuala
Professor of Molecular Medicine
A. I. Virtanen Institute
University of Eastern Finland
P.O.Box 1627, Kuopio
FIN-70211, Finland
Tel: +358403552075
E-mail: [email protected]

Received date: August 05, 2013; Accepted date:August 19, 2013; Published date: August 21, 2013

Citation: Tuppurainen L, Sallinen H, Hakkarainen H, Liimatainen T, Hassan M, et al. (2013) Functional MRI Measurements to Predict Early Adenoviral Gene Therapy Response in Ovarian Cancer Mouse Model. J Genet Syndr Gene Ther 4:171. doi: 10.4172/2157-7412.1000171

Copyright: © 2013 Tuppurainen L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Anti-angiogenic and anti-lymphangiogenic gene therapy is a new potential method for the treatment of epithelial ovarian carcinoma. We studied the usefulness and feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) and relaxation measurements as surrogate markers of AdsVEGFR-2, AdsVEGFR-3, AdsNRP-1 and AdsNRP-2 gene therapy treatment responses in an intraperitoneal ovarian cancer mouse model (n= 45). Gene therapy was also combined with paclitaxel and carboplatin chemotherapy. Gene therapy was performed when visible tumors were noticed in MRI. Adenoviral gene transfer was dosed intravenously (2×109 pfu), while chemotherapy was dosed intraperitoneally. The study groups were: AdLacZ as controls (group I); AdsVEGFR-2 and AdsVEGFR-3 (group II); combination of AdsVEGFR-2, AdsVEGFR-3 and chemotherapy (group III) and AdsNRP-1 and AdsNRP-2 (group IV). Antitumor effectiveness was assessed by sequential MRI, immunohistochemistry, microvessel density, overall tumor growth, formation of ascites and survival time. Early responses in tumor tissue were evaluated with MRI measurements using relaxation times T2, T1ρ, TRAFF2, TRAFF4 and water apparent diffusion coefficient (ADC). The mean survival of mice (30 days) was significantly prolonged in group II as compared to controls (24 days) or other treatment groups (p= 0.003). The mean vascular density (MVD) and total vascular area (TVA) were significantly lower compared to controls in all groups: group II (p= 0.001), group III (p= 0.002), group IV (p= 0.026). T2 relaxation times were significantly increased at day 8 after the gene transfer in the combination gene therapy and chemotherapy group III compared to controls (p= 0.005). ADC values in the tumors were significantly increased in group IV at four days compared to controls (p= 0.044). Early changes in T2 relaxation times and ADC values after gene therapy suggest the potential of T2 relaxation time measurements and DW-MRI as early markers of treatment response after anti-angiogenic gene therapy and chemotherapy.

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