Details

Autor(en) / Beteiligte

• Gade, Terence P.F.
• Koutcher, Jason A.
• Spees, William M.
• Beattie, Bradley J.
• Ponomarev, Vladimir
• Doubrovin, Michael
• Buchanan, Ian M.
• Beresten, Tatiana
• Zakian, Kristen L.
• Le, H. Carl
• Tong, William P.
• Mayer-Kuckuk, Philipp
• Blasberg, Ronald G.
• Gelovani, Juri G.

Titel

Imaging Transgene Activity

Ist Teil von

• Cancer research (Chicago, Ill.), 2008-04, Vol.68 (8), p.2878-2884

Erscheinungsjahr

2008

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. While current imaging permits the non-invasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. Magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase-uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT+ cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of this enzyme. This study presents a translational imaging strategy for precise, in vivo measurements of transgene activity with potential applications in both pre-clinical and clinical settings.