title: Imaging transgene activity in vivo.
abstract: 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. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo 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 the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Terence P F
authors.initials: TP
authors.lastname: Gade
authors.forename: Jason A
authors.initials: JA
authors.lastname: Koutcher
authors.forename: William M
authors.initials: WM
authors.lastname: Spees
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Beattie
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ponomarev
authors.forename: Michael
authors.initials: M
authors.lastname: Doubrovin
authors.forename: Ian M
authors.initials: IM
authors.lastname: Buchanan
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beresten
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Zakian
authors.forename: H Carl
authors.initials: HC
authors.lastname: Le
authors.forename: William P
authors.initials: WP
authors.lastname: Tong
authors.forename: Philipp
authors.initials: P
authors.lastname: Mayer-Kuckuk
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Blasberg
authors.forename: Juri G
authors.initials: JG
authors.lastname: Gelovani
mesh_terms: D000818:Animals; D002279:Carcinoma 256, Walker / Q000473:pathology; D045744:Cell Line, Tumor; D005461:Fluorine; D015316:Genetic Therapy / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D019076:Transgenes; D014183:Transplantation, Heterologous / Q000379:methods / Q000473:pathology
chemical_list: D005461:Fluorine