PURPOSE: To assess the optimal reporter probe/reporter gene combination for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression, we compared the cellular uptake of 1-(2'-fluoro-2'-deoxy-D-arabinofuranosyl)-5-methyluracil (FMAU), 2'-fluoro-2'-deoxyarabinofuranosyl-5-ethyluracil (FEAU), 2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl-5-iodouracil (FIAU) and penciclovir (PCV) in both HSV1-tk and HSV1-sr39tk expressing cells. PROCEDURES: For stably transfected cell studies, C6 rat glioma cells, C6 HSV1-tk transfectant, C6 mutant HSV1-sr39tk transfectant, rat Morris hepatoma cells (MH3924A), and MH3924A HSV1-tk transfectant cells were used. For adenoviral infection studies, C6 rat glioma cells were exposed to serial titers of AdCMV-HSV1-tk, AdCMV-HSV1-sr39tk, or AdCMV-fluc for 24 hours. These cells were incubated with [(14)C]FMAU, [(3)H]FEAU, [(14)C]FIAU, and [(3)H]PCV, and cellular uptake of radioactivity was measured. RESULTS: [(3)H]FEAU exhibited the highest or second highest accumulation and the most selectivity regardless of the mode of gene transfer for both HSV1-tk and mutant HSV1-sr39tk reporter genes. CONCLUSION: This combination of high accumulation and high selectivity for both HSV1-tk and HSV1-sr39tk makes suitably radiolabeled FEAU a promising candidate as a radiotracer for imaging HSV1-tk/HSV1-sr39tk gene expression in living subjects.
PURPOSE: To assess the optimal reporter probe/reporter gene combination for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression, we compared the cellular uptake of 1-(2'-fluoro-2'-deoxy-D-arabinofuranosyl)-5-methyluracil (FMAU), 2'-fluoro-2'-deoxyarabinofuranosyl-5-ethyluracil (FEAU), 2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl-5-iodouracil (FIAU) and penciclovir (PCV) in both HSV1-tk and HSV1-sr39tk expressing cells. PROCEDURES: For stably transfected cell studies, C6 ratglioma cells, C6 HSV1-tk transfectant, C6 mutant HSV1-sr39tk transfectant, ratMorris hepatoma cells (MH3924A), and MH3924A HSV1-tk transfectant cells were used. For adenoviral infection studies, C6 ratglioma cells were exposed to serial titers of AdCMV-HSV1-tk, AdCMV-HSV1-sr39tk, or AdCMV-fluc for 24 hours. These cells were incubated with [(14)C]FMAU, [(3)H]FEAU, [(14)C]FIAU, and [(3)H]PCV, and cellular uptake of radioactivity was measured. RESULTS: [(3)H]FEAU exhibited the highest or second highest accumulation and the most selectivity regardless of the mode of gene transfer for both HSV1-tk and mutant HSV1-sr39tk reporter genes. CONCLUSION: This combination of high accumulation and high selectivity for both HSV1-tk and HSV1-sr39tk makes suitably radiolabeled FEAU a promising candidate as a radiotracer for imaging HSV1-tk/HSV1-sr39tk gene expression in living subjects.
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Authors: T C Chou; X B Kong; M P Fanucchi; Y C Cheng; K Takahashi; K A Watanabe; J J Fox Journal: Antimicrob Agents Chemother Date: 1987-09 Impact factor: 5.191
Authors: Juri Gelovani Tjuvajev; Mikhail Doubrovin; Timothy Akhurst; Shangde Cai; Julius Balatoni; Mian M Alauddin; Ronald Finn; William Bornmann; Howard Thaler; Peter S Conti; Ronald G Blasberg Journal: J Nucl Med Date: 2002-08 Impact factor: 10.057
Authors: Kevin W Morin; Weili Duan; Lihua Xu; Aihua Zhou; Sameh Moharram; Edward E Knaus; Alexander J B McEwan; Leonard I Wiebe Journal: Nucl Med Biol Date: 2004-07 Impact factor: 2.408
Authors: J L Abbruzzese; S Schmidt; M N Raber; J K Levy; A M Castellanos; S S Legha; I H Krakoff Journal: Invest New Drugs Date: 1989-07 Impact factor: 3.850