ArticleEuropean journal of nuclear medicine and molecular imaging2009
PET imaging of HSV1-tk mutants with acquired specificity toward pyrimidine- and acycloguanosine-based radiotracers.
Article in European journal of nuclear medicine and molecular imaging, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 18 citations in OpenAlex.
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- Enhancement of PSMA-Directed CAR Adoptive Immunotherapy by PD-1/PD-L1 Blockade.Molecular therapy oncolytics · 2017Article
- Redesigning human 2'-deoxycytidine kinase enantioselectivity for L-nucleoside analogues as reporters in positron emission tomography.ACS chemical biology · 2014Article
- In vivo imaging of therapy-induced anti-cancer immune responses in humans.Cellular and molecular life sciences : CMLS · 2013Review
- Positron emission tomography reporter genes and reporter probes: gene and cell therapy applications.Theranostics · 2012Article
- A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase suitable for PET during treatment with acycloguanosine-based cytotoxic drugs.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2010Article
- Modular strategies for PET imaging agents.Current opinion in chemical biology · 2010Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe aim of this study was to create an alternative mutant of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene with reduced phosphorylation capacity for acycloguanosine derivatives, but not pyrimidine-based compounds that will allow for successful PET imaging.
methodsA new mutant of HSV1-tk reporter gene, suitable for PET imaging using pyrimidine-based radiotracers, was developed. The HSV1-tk mutant contains an arginine-to-glutamine substitution at position 176 (HSV1-R176Qtk) of the nucleoside binding region of the enzyme.
resultsThe mutant-gene product showed favorable enzymatic characteristics toward pyrimidine-based nucleosides, while exhibiting reduced activity with acycloguanosine derivatives. In order to enhance HSV1-R176Qtk reporter activity with pyrimidine-based radiotracers, we introduced the R176Q substitution into the more active HSV1-sr39tk mutant. U87 human glioma cells transduced with the HSV1-R176Qsr39tk double mutant reporter gene showed high (3)H-FEAU pyrimidine nucleoside and low (3)H-penciclovir acycloguanosine analog uptake in vitro. PET imaging also demonstrated high (18)F-FEAU and low (18)F-FHBG accumulation in HSV1-R176Qsr39tk+ xenografts. The feasibility of imaging two independent nucleoside-specific HSV1-tk mutants in the same animal with PET was demonstrated. Two opposite xenografts expressing the HSV1-R176Qsr39tk reporter gene and the previously described acycloguanosine-specific mutant of HSV1-tk, HSV1-A167Ysr39tk reporter gene, were imaged using a short-lived pyrimidine-based (18)F-FEAU and an acycloguanosine-based (18)F-FHBG radiotracer, respectively, administered on 2 consecutive days.
conclusionWe conclude that in combination with acycloguanosine-specific HSV1-A167Ysr39tk reporter gene, a HSV1-tk mutant containing the R176Q substitution could be used for PET imaging of two different cell populations or concurrent molecular biological processes in the same living subject.
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