Imaging of HSV-tk reporter gene expression: Comparison between [ 18F]FEAU, [18F]FFEAU, and other imaging probes Journal Article


Authors: Miyagawa, T.; Gogiberidze, G.; Serganova, I.; Cai, S.; Balatoni, J. A.; Thaler, H. T.; Ageyeva, L.; Pillarsetty, N.; Finn, R. D.; Blasberg, R. G.
Article Title: Imaging of HSV-tk reporter gene expression: Comparison between [ 18F]FEAU, [18F]FFEAU, and other imaging probes
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-b-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. Copyright © 2008 by the Society of Nuclear Medicine, Inc.
Keywords: controlled study; unclassified drug; drug penetration; nonhuman; comparative study; positron emission tomography; radiopharmaceuticals; animal cell; animals; animal tissue; gene expression profiling; animal experiment; in vivo study; cancer cell culture; in vitro study; cell line, tumor; drug distribution; drug uptake; isotope labeling; guanosine derivative; rat; arabinofuranosyluracil; reporter gene; thymidine kinase; genes, reporter; herpesvirus 1, human; rats; tracer; pet; herpes simplex virus; molecular probe; enzyme assay; feau; hsv1-tk; fluorine radioisotopes; fiau; 18f; pyrimidine nucleoside derivative; ffeau; herpes simplex virus type 1 thymidine kinase; 1 (2' deoxy 2' fluoro beta dextro arabinofuranosyl) 5 (2 fluoroethyl)uridine f 18; 1 (2' deoxy 2' fluoro beta dextro arabinofuranosyl) 5 ethyluridine f 18; 1 (2' deoxy 2' fluoro beta dextro arabinofuranosyl) 5 ethyluridine h 3; 2' fluoro 2' deoxy 5' iodo 1beta dextro arabinofuranosyluracil c 14; 2' fluoro 2' deoxy 5' iodo 1beta dextro arabinofuranosyluracil i 124; 9 [(3 fluoro 1 hydroxy 2 propoxy)methyl]guanine f 18; 9 {4 fluoro 3 hydroxymethylbutyl)guanine f 18; thymidine derivative
Journal Title: Journal of Nuclear Medicine
Volume: 49
Issue: 4
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2008-04-01
Start Page: 637
End Page: 648
Language: English
DOI: 10.2967/jnumed.107.046227
PUBMED: 18344433
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Ronald G Blasberg
    272 Blasberg
  2. Ronald D Finn
    279 Finn
  3. Shangde Cai
    42 Cai
  4. Howard T Thaler
    245 Thaler
  5. Lyudmila Ageyeva
    31 Ageyeva