Imaging of HSV-tk Reporter Gene Expression: Comparison Between [18F]FEAU, [18F]FFEAU, and Other Imaging Probes
Open Access
- 14 March 2008
- journal article
- research article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 49 (4), 637-648
- https://doi.org/10.2967/jnumed.107.046227
Abstract
Herpes virus type 1 thymidine kinase (HSV1-tk) and the mutant HSV1-sr39tk are the 2 most widely used “reporter genes” for radiotracer-based imaging. Two pyrimidine nucleoside analogs, [18F]FEAU (1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-ethyluridine) and [18F]FFEAU (1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-(2-fluoroethyl)uridine), have generated recent interest as potential new probes for imaging HSV1-tk and HSV1-sr39tk gene expression. Methods: We compared [18F]FEAU and [18F]FFEAU with a series of other pyrimidine nucleoside derivatives (including 1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-iodouridine [FIAU]) and with acycloguanosine analogs using a stable HSV1-tk transduced cell line (RG2TK+) and wild-type RG2 cells. Results: The in vitro accumulation data and the calculated and normalized clearance constant, nKi, as well as sensitivity and selectivity indices indicated that 2 pyrimidine nucleoside probes, [18F]FEAU and [18F]FFEAU, had the best uptake characteristics. These probes were selected for further dynamic PET studies in nude rats bearing subcutaneous RG2TK+ and RG2 tumors. The 2-h postinjection [18F]FEAU uptake levels were 3.3% ± 1.0% and 0.28% ± 0.07% dose/cm3 in subcutaneous RG2TK+ and RG2 tumors, respectively, and 2.3% ± 0.2% and 0.19% ± 0.01% dose/cm3, respectively, for [18F]FFEAU. The corresponding RG2TK+/RG2 uptake ratios were 11.5 ± 1.5 and 12.2 ± 1.4, respectively. The inherent problem of comparing different radiolabeled pyrimidine nucleoside and guanosine-based probes for imaging HSV1-tk expression using different transduced cell lines and assay systems in the absence of an independent thymidine kinase–enzyme assay is discussed. Conclusion: For HSV1-tk reporter systems that require a 1- to 4-h PET paradigm, HSV1-tk-[18F]FEAU is the current top contender.This publication has 24 references indexed in Scilit:
- Human reporter genes: potential use in clinical studiesNuclear Medicine and Biology, 2007
- Construction and Validation of Improved Triple Fusion Reporter Gene Vectors for Molecular Imaging of Living SubjectsCancer Research, 2007
- 18F-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression: in-vitro comparison with other PET tracersNuclear Medicine Communications, 2006
- Comparison of [14C]FMAU, [3H]FEAU, [14C]FIAU, and [3H]PCV for Monitoring Reporter Gene Expression of Wild Type and Mutant Herpes Simplex Virus Type 1 Thymidine Kinase in Cell CultureMolecular Imaging & Biology, 2005
- Molecular Imaging of Temporal Dynamics and Spatial Heterogeneity of Hypoxia-Inducible Factor-1 Signal Transduction Activity in Tumors in Living MiceCancer Research, 2004
- A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imagingEuropean Journal of Nuclear Medicine and Molecular Imaging, 2004
- Direct Comparison of Radiolabeled Probes FMAU, FHBG, and FHPG as PET Imaging Agents for HSV1-tk Expression in a Human Breast Cancer ModelMolecular Imaging, 2004
- Comparison of [ 18 F]FHBG and [ 14 C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfectionEuropean Journal of Nuclear Medicine and Molecular Imaging, 2003
- Complex regulation of nucleoside transporter expression in epithelial and immune system cellsMolecular Membrane Biology, 2001
- Transcriptional Activation of Thymidine Kinase, a Marker for Cell Cycle ControlProgress in Nucleic Acid Research and Molecular Biology, 1996