Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors

Gene Ther. 2001 Jul;8(14):1072-80. doi: 10.1038/


Biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (PET) reporter gene (PRG) and then imaging the PRG's expression by a PET reporter probe (PRP) in living animals. We validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the PRG, to track the therapeutic gene's expression. Two PET reporter genes, a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) and dopamine-2 receptor (D(2)R), each regulated by the same cytomegalovirus (CMV) promoter, have been inserted into separate adenoviral vectors (Ad). We demonstrate that cells co-infected with equivalent titers of Ad-CMV-HSV1-sr39tk and Ad-CMV-D(2)R express both reporter genes with good correlation (r(2) = 0.93). Similarly, a high correlation (r(2) = 0.97) was observed between the expression of both PRGs in the livers of mice co-infected via tail-vein injection with equivalent titers of these two adenoviruses. Finally, microPET imaging of HSV1-sr39tk and D(2)R expression with 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine ([(18)F]FHBG) and 3-(2-[(18)F]fluoroethyl)spiperone ([(18)F]FESP), utilizing several adenovirus-mediated delivery routes, illustrates the feasibility of evaluating relative levels of transgene expression in living animals, using this approach.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • COS Cells
  • Cells, Cultured
  • Cytomegalovirus / genetics*
  • Feasibility Studies
  • Gene Expression
  • Genetic Vectors / administration & dosage
  • Guanine / analogs & derivatives
  • Herpesvirus 1, Human / enzymology*
  • Liver / diagnostic imaging
  • Mice
  • Mice, Inbred Strains
  • Mice, Nude
  • Promoter Regions, Genetic*
  • Rats
  • Receptors, Dopamine D2 / genetics*
  • Spiperone / analogs & derivatives
  • Thymidine Kinase / genetics*
  • Time Factors
  • Tomography, Emission-Computed*


  • 9-(4-fluoro-3-hydroxymethylbutyl)guanine
  • Receptors, Dopamine D2
  • 3-N-(2-fluoroethyl)spiperone
  • Spiperone
  • Guanine
  • Thymidine Kinase