Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal.
Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem gamma counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem gamma counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.
Cancer Research UK Molecular Oncology Unit, London W12 0NN, UK.
Thomas
T
Groot-Wassink
Eric O
EO
Aboagye
Yaohe
Y
Wang
Nicholas R
NR
Lemoine
Andrew J
AJ
Reader
Georges
G
Vassaux
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D007454:Iodides; D008024:Ligands; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D014055:Tomography, Emission-Computed; D019076:Transgenes; D000099209:Sodium-Iodide Symporters
D018076:DNA, Complementary; D007454:Iodides; D008024:Ligands; D027981:Symporters; D000099209:Sodium-Iodide Symporters