Imaging transgene activity in vivo.
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.
Gade
Terence P F
TP
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Koutcher
Jason A
JA
Spees
William M
WM
Beattie
Bradley J
BJ
Ponomarev
Vladimir
V
Doubrovin
Michael
M
Buchanan
Ian M
IM
Beresten
Tatiana
T
Zakian
Kristen L
KL
Le
H Carl
HC
Tong
William P
WP
Mayer-Kuckuk
Philipp
P
Blasberg
Ronald G
RG
Gelovani
Juri G
JG
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
D005461:Fluorine