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Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene.
- Source :
-
Human gene therapy [Hum Gene Ther] 2002 Sep 20; Vol. 13 (14), pp. 1723-35. - Publication Year :
- 2002
-
Abstract
- Amongst the various methods that can be developed for noninvasive monitoring of gene expression in vivo, the use of positron emission tomography (PET) appears to be the most promising both for preclinical and clinical studies. Various genes have been described as potential PET reporters, but there is a need to develop new approaches that exploit transgenes with both therapeutic and imaging potential. The Na/I symporter (NIS) gene is expressed mainly in the thyroid and is responsible for iodide accumulation in this organ. The NIS gene has been used in gene therapy experimentation. Ectopic expression of this gene in various type of malignant cells has led to radiosensitization and in some cases tumor regression in xenograft models in nude mice, highlighting the therapeutic potential of this approach. In the present study, we demonstrate the potential of the human NIS gene (hNIS) as a reporter gene. Expression of hNIS, after plasmid transfection or adenoviral gene delivery, can be monitored in vitro on incubation with (125)I. Iodide uptake in the transduced cells can be directly correlated with the levels of gene expression in vitro. Ectopic expression of the NIS gene in vivo can be monitored in biodistribution studies on intravenous injection of (125)I. Adenovirus delivery induces gene expression essentially in the liver, adrenal glands, lungs, pancreas, and spleen. Expression of hNIS in tumor xenograft models can also be detected when the virus is injected intratumorally. Finally, hNIS expression was monitored by PET after intravenous injection of (124)I, demonstrating the potential of this approach for noninvasive imaging.
- Subjects :
- Adenocarcinoma pathology
Adenoviruses, Human genetics
Animals
DNA, Complementary genetics
DNA, Recombinant genetics
Gene Expression
Genetic Vectors analysis
Genetic Vectors genetics
Humans
Injections, Intravenous
Iodine metabolism
Iodine Radioisotopes analysis
Ion Transport drug effects
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Pancreatic Neoplasms pathology
Perchlorates pharmacology
Recombinant Fusion Proteins antagonists & inhibitors
Recombinant Fusion Proteins biosynthesis
Recombinant Fusion Proteins physiology
Sodium metabolism
Sodium Compounds pharmacology
Symporters antagonists & inhibitors
Symporters biosynthesis
Symporters physiology
Tissue Distribution
Transduction, Genetic
Transplantation, Heterologous
Tumor Cells, Cultured virology
Adenoviruses, Human isolation & purification
Genes, Reporter
Genetic Vectors pharmacokinetics
Symporters genetics
Tomography, Emission-Computed
Subjects
Details
- Language :
- English
- ISSN :
- 1043-0342
- Volume :
- 13
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Human gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 12396625
- Full Text :
- https://doi.org/10.1089/104303402760293565