title: Positron emission tomography imaging of adenoviral-mediated transgene expression in liver cancer patients.
abstract: OBJECTIVE
  In gene-therapy protocols, imaging of gene expression is needed to evaluate the transduction efficiency of the vector, its tissue distribution, and the duration of transgene expression and to assess the feasibility of repeated vector administration.
  
  
  METHODS
  We have used positron emission tomography with a fluorine-18-labeled penciclovir analogue to monitor thymidine kinase gene expression after intratumoral injection of a first-generation recombinant adenovirus in patients with hepatocellular carcinoma. Patients were enrolled in a pilot clinical trial and treated with escalating doses of the vector. Two days after adenovirus inoculation, transgene expression was evaluated during the first hours after administration of the radiotracer both on the treated lesion and on a whole-body basis.
  
  
  RESULTS
  Transgene expression in the tumor was dependent on the injected dose of the adenovirus and was detectable in all patients who received > or = 10(12) viral particles. However, when the study was repeated 9 days after vector injection, no expression could be observed. It is interesting to note that no specific expression of the transgene could be detected in distant organs or in the surrounding cirrhotic tissue in any of the cases studied.
  
  
  CONCLUSIONS
  Our findings show the real possibility of imaging transgene expression in humans by using viral vectors. We show that hepatocarcinoma is a permissive tumor for adenoviral infection and that the nontumoral cirrhotic liver is spared from transduction when the vector is administered by intratumoral injection. These results show that positron emission tomography imaging may help in the design of gene-therapy strategies and in the clinical assessment of new-generation vectors.
authors.affiliation: Department of Nuclear Medicine, Clínica Universitaria de Navarro, Pamplona, Spain. ipenuelas@unav.es
authors.forename: Iván
authors.initials: I
authors.lastname: Peñuelas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: José F
authors.initials: JF
authors.lastname: Boán
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.forename: Josep
authors.initials: J
authors.lastname: Martí-Climent
authors.forename: María
authors.initials: M
authors.lastname: Ruiz
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: José A
authors.initials: JA
authors.lastname: Richter
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000235:genetics / Q000628:therapy*; D005462:Fluorine Radioisotopes; D020869:Gene Expression Profiling; D015316:Genetic Therapy; D005822:Genetic Vectors; D006147:Guanine / Q000031:analogs & derivatives*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000628:therapy*; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D005462:Fluorine Radioisotopes; D006147:Guanine; D013937:Thymidine Kinase