PET imaging of transgene expression

Duncan C. MacLaren, Tatsushi Toyokuni, Simon R Cherry, Jorge R. Barrio, Michael E. Phelps, Harvey R. Herschman, Sanjiv S. Gambhir

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

A vital step in transgenic animal study and gene therapy is the ability to assay the extent of transgene expression. Unfortunately, classic methods of assaying transgene expression require biopsies or death of the subject. We are developing techniques to noninvasively and repetitively determine the location, duration, and magnitude of transgene expression in living animals. This will allow investigators and clinicians to assay the effectiveness of their particular experimental and therapeutic paradigms. Of radionuclide (single photon emission computed tomography, positron emission tomography [PET]), optical (green fluorescent protein, luciferase), and magnetic (magnetic resonance imaging) approaches, only the radionuclide approach has sufficient sensitivity and quantitation to measure the expression of genes in vivo. We describe the instrumentation involved in high resolution PET scanning. We also describe the principles of PET reporter gene/reporter probe in vivo imaging, the development of two in vivo reporter gene imaging systems, and the validation of our ability to noninvasively, quantitatively, and repetitively image gene expression in murine viral gene transfer and transgenic models. We compare the two reporter gene systems and discuss their utility for the study of transgenic animals and gene therapies. Finally, we mention alternative approaches to image gene expression by using radiolabeled antibody fragments to image specific proteins and radiolabeled oligonucleotides to image RNA messages directly. (C) 2000 Society of Biological Psychiatry.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalBiological Psychiatry
Volume48
Issue number5
DOIs
StatePublished - Sep 1 2000

Keywords

  • Dopamine 2 receptor
  • Gene expression
  • Herpes simplex virus thymidine kinase
  • PET
  • Reporter gene
  • Transgene imaging

ASJC Scopus subject areas

  • Biological Psychiatry

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  • Cite this

    MacLaren, D. C., Toyokuni, T., Cherry, S. R., Barrio, J. R., Phelps, M. E., Herschman, H. R., & Gambhir, S. S. (2000). PET imaging of transgene expression. Biological Psychiatry, 48(5), 337-348. https://doi.org/10.1016/S0006-3223(00)00970-7