The use of high-frequency ultrasound imaging and biofluorescence for in vivo evaluation of gene therapy vectors

BMC Medical Imaging

P Louise Coletta¹  Adrian Whitehouse³  Alexander F Markham¹  Ian M Carr¹  Nigel Scott²  Gemma Marston¹  Stuart A Macnab³  Nicola Ingram¹ 

[1] School of Medicine, University of Leeds Brenner Building, St James’s University Hospital, Leeds LS9 7TF, UK;Department of Histopathology, Bexley Wing, St James’s University Hospital, Leeds LS9 7TF, UK;School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK

关键词: Colorectal cancer;    Multi-modal;    Imaging;    Gene therapy;    Ultrasound;    Biofluorescence;   

Others  :  1090469
DOI  :  10.1186/1471-2342-13-35

 received in 2013-02-01, accepted in 2013-11-01,  发布年份 2013

【 摘 要 】

Background

Non-invasive imaging of the biodistribution of novel therapeutics including gene therapy vectors in animal models is essential.

Methods

This study assessed the utility of high-frequency ultrasound (HF-US) combined with biofluoresence imaging (BFI) to determine the longitudinal impact of a Herpesvirus saimiri amplicon on human colorectal cancer xenograft growth.

Results

HF-US imaging of xenografts resulted in an accurate and informative xenograft volume in a longitudinal study. The volumes correlated better with final ex vivo volume than mechanical callipers (R² = 0.7993, p = 0.0002 vs. R² = 0.7867, p = 0.0014). HF-US showed that the amplicon caused lobe formation. BFI demonstrated retention and expression of the amplicon in the xenografts and quantitation of the fluorescence levels also correlated with tumour volumes.

Conclusions

The use of multi-modal imaging provided useful and enhanced insights into the behaviour of gene therapy vectors in vivo in real-time. These relatively inexpensive technologies are easy to incorporate into pre-clinical studies.

【 授权许可】

   
2013 Ingram et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Waerzeggers Y, et al.: Methods to monitor gene therapy with molecular imaging. Methods 2009, 48(2):146-160.
• [2]Cheung AM, et al.: Three-dimensional ultrasound biomicroscopy for xenograft growth analysis. Ultrasound Med Biol 2005, 31(6):865-870.
• [3]Samee A, Selvasekar CR: Current trends in staging rectal cancer. World J Gastroenterol 2011, 17(7):828-834.
• [4]Abdelrahman MA, et al.: High-Frequency Ultrasound for In Vivo Measurement of Colon Wall Thickness in Mice. Ultrasound Med Biol 2012, 38(3):432-442.
• [5]Lee DJ, et al.: Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model. J Ultrasound Med 2008, 27(6):855-866.
• [6]Zhao Y, et al.: Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers. Mol Cell Biochem 2011, 353(1–2):93-99.
• [7]Euhus DM, et al.: Tumor measurement in the nude mouse. J Surg Oncol 1986, 31(4):229-234.
• [8]Sims K, et al.: In vitro evaluation of a 'stealth’ adenoviral vector for targeted gene delivery to adult mammalian neurones. J Gene Med 2009, 11(4):335-344.
• [9]Smith PG, et al.: Herpesvirus saimiri-based vector biodistribution using noninvasive optical imaging. Gene Ther 2005, 12(19):1465-1476.
• [10]Prasad KM, et al.: Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution. Gene Ther 2011, 18(1):43-52.
• [11]Rehemtulla A, et al.: Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2000, 2(6):491-495.
• [12]Yang M, et al.: Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci U S A 2000, 97(3):1206-1211.
• [13]Snyder C, et al.: Complementarity of ultrasound and fluorescence imaging in an orthotopic mouse model of pancreatic cancer. BMC Cancer 2009, 9(1):106.
• [14]Abou-Elkacem L, et al.: Comparison of muCT, MRI and optical reflectance imaging for assessing the growth of GFP/RFP-expressing tumors. Anticancer Res 2011, 31(9):2907-2913.
• [15]Smith PG, et al.: Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures. Cancer Gene Ther 2005, 12(3):248-256.
• [16]Macnab SA, et al.: Herpesvirus saimiri-mediated delivery of the adenomatous polyposis coli tumour suppressor gene reduces proliferation of colorectal cancer cells. Int J Oncol 2011, 39(5):1173-1181.
• [17]Tomayko MM, Reynolds CP: Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 1989, 24(3):148-154.
• [18]Ayers GD, et al.: Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements. J Ultrasound Med 2010, 29(6):891-901.
• [19]Jensen MM, et al.: Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. BMC Med Imaging 2008, 8:16. BioMed Central Full Text
• [20]Keller MD, et al.: Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis. Lasers Surg Med 2010, 42(1):15-23.