Molecular PET imaging of HSV1-tk reporter gene expression using [18F]FEAU

Nat Protoc. 2007;2(2):416-23. doi: 10.1038/nprot.2007.49.

Abstract

Non-invasive imaging of transgene expression requires the appropriate combination of a reporter gene and a reporter probe. [18F]FEAU positron emission tomography (PET) is used for the assessment of herpes simplex virus type-1 thymidine kinase gene expression. Hybrid AAV phage (termed AAVP) can be adapted to transduce mammalian cells by targeting to a specific receptor. We evaluated a targeted AAVP vector using [18F]FEAU PET. This protocol describes [18F]FEAU production and dosing, micro-PET imaging and image analysis. 2-Deoxy-2-trifluoromethanesulfonyl-1,3,5-tri-O-benzoyl-alpha-D-ribofuranose is radio-fluorinated, converted into its 1-bromo derivative and coupled with protected 5-ethyl uracil. The coupled product is hydrolyzed and purified using HPLC. Tumor-bearing animals targeted with either retroviral or AAVP vectors are anesthetized and injected with [18F]FEAU (0.1 mCi per mouse); this is followed 2 h after injection by imaging on a micro-PET. Production of [18F]FEAU requires approximately 3.5 h from the end of bombardment. PET imaging studies require 2-3 h (depending on the number of animals) after synthesis of [18F]FEAU.

MeSH terms

  • Animals
  • Arabinofuranosyluracil / analogs & derivatives
  • Cell Line, Tumor
  • Fluorine Radioisotopes
  • Gene Expression Profiling / methods*
  • Gene Targeting
  • Genes, Reporter / genetics*
  • Genetic Vectors
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / metabolism
  • Humans
  • Mice
  • Molecular Structure
  • Positron-Emission Tomography / methods*
  • Thymidine Kinase / metabolism*
  • Transgenes / genetics

Substances

  • Fluorine Radioisotopes
  • Arabinofuranosyluracil
  • 2'-fluoro-5-ethylarabinosyluracil
  • Thymidine Kinase