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Radiolabeled nucleoside analogues for PET imaging of HSV1-tk gene expression

Mian M Alauddin1, Juri G Gelovani

  • 1The University of Texas MD Anderson Cancer Center, Houston, TX, USA. alauddin@mdanderson.org

Current Topics in Medicinal Chemistry
|June 30, 2010
PubMed

Insights

Monitoring Herpes Simplex Virus type 1 thymidine kinase (HSV1-tk) activity in vivo is crucial for optimizing gene therapy. Positron emission tomography (PET) imaging with nucleoside analogues offers a noninvasive method to track HSV1-tk gene expression and distribution.

Area of Science:

  • Molecular Biology
  • Biotechnology
  • Medical Imaging

Background:

  • The Herpes Simplex Virus type 1 thymidine kinase (HSV1-tk) gene is utilized as a reporter and suicide gene in molecular imaging and cancer gene therapy.
  • Clinical gene therapy protocols involving HSV1-tk require optimization, necessitating in vivo monitoring of gene activity.

Purpose of the Study:

  • To review methods for in vivo monitoring of HSV1-tk enzyme activity using Positron Emission Tomography (PET).
  • To present information on radiolabeling and PET imaging of HSV1-tk gene expression with various nucleoside analogues.

Main Methods:

  • Review of radiolabeled nucleoside analogues as reporter probes for HSV-TK enzyme activity.
  • Discussion of Positron Emission Tomography (PET) imaging principles for gene expression monitoring.

Main Results:

  • Development of several radiolabeled pyrimidine (thymidine) and purine (acycloguanosine) derivatives for PET imaging of HSV-TK activity.
  • PET imaging allows noninvasive quantification of gene expression extent and distribution with high resolution and sensitivity.

Conclusions:

  • In vivo monitoring of HSV1-tk activity via PET is essential for optimizing gene therapy protocols.
  • Radiolabeled nucleoside analogues serve as effective probes for PET imaging of HSV1-tk gene expression.

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