{"doi":"10.1073/pnas.97.6.2785","title":"A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography","abstract":"<jats:p>\n                    We are developing assays for noninvasive, quantitative imaging of reporter genes with positron emission tomography (PET), for application both in animal models and in human gene therapy. We report here a method to improve the detection of lower levels of PET reporter gene expression by utilizing a\n                    <jats:italic>mutant</jats:italic>\n                    herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) as a PET reporter gene. The HSV1-sr39tk mutant was identified from a library of site-directed mutants. Accumulation (net uptake) of the radioactively labeled substrates [8-\n                    <jats:sup>3</jats:sup>\n                    H]penciclovir ([8-\n                    <jats:sup>3</jats:sup>\n                    H]PCV), and 8-[\n                    <jats:sup>18</jats:sup>\n                    F]fluoropenciclovir (FPCV) in C6 rat glioma cells expressing HSV1-sr39tk is increased by a factor of ≈2.0 when compared with C6 cells expressing wild-type HSV1-tk. The increased imaging sensitivity of HSV1-sr39tk when FPCV is used is also demonstrated\n                    <jats:italic>in vivo</jats:italic>\n                    both with tumor cells stably transfected with either HSV1-tk or HSV1-sr39tk, and after hepatic delivery of HSV1-tk or HSV1-sr39tk by using adenoviral vectors. The use of HSV1-sr39tk as a PET reporter gene and FPCV as a PET reporter probe results in significantly enhanced sensitivity for imaging reporter gene expression\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":636452,"datarank":0.919357531509082,"base_score":6.129050210060545,"endowment":6.129050210060545,"self_citation_contribution":0.919357531509082,"citation_network_contribution":0.0,"self_endowment_contribution":0.919357531509082,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":458,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1651868,"name":"Eileen Bauer","orcid":null,"position":1,"is_corresponding":false},{"id":363966,"name":"Margaret E. Black","orcid":"0000-0002-3152-5112","position":2,"is_corresponding":false},{"id":535108,"name":"Qianwa Liang","orcid":"0000-0003-1473-9749","position":3,"is_corresponding":false},{"id":1651869,"name":"Mark S. Kokoris","orcid":null,"position":4,"is_corresponding":false},{"id":1302147,"name":"Jorge R. Barrio","orcid":null,"position":5,"is_corresponding":false},{"id":1629771,"name":"Meera Iyer","orcid":null,"position":6,"is_corresponding":false},{"id":1651870,"name":"Mohammad Namavari","orcid":null,"position":7,"is_corresponding":false},{"id":1583203,"name":"Michael E. Phelps","orcid":null,"position":8,"is_corresponding":false},{"id":272954,"name":"Harvey R. Herschman","orcid":null,"position":9,"is_corresponding":false},{"id":232231,"name":"Sanjiv S. Gambhir","orcid":"0000-0002-2711-7554","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography","abstract":"<jats:p>\n                    We are developing assays for noninvasive, quantitative imaging of reporter genes with positron emission tomography (PET), for application both in animal models and in human gene therapy. We report here a method to improve the detection of lower levels of PET reporter gene expression by utilizing a\n                    <jats:italic>mutant</jats:italic>\n                    herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) as a PET reporter gene. The HSV1-sr39tk mutant was identified from a library of site-directed mutants. Accumulation (net uptake) of the radioactively labeled substrates [8-\n                    <jats:sup>3</jats:sup>\n                    H]penciclovir ([8-\n                    <jats:sup>3</jats:sup>\n                    H]PCV), and 8-[\n                    <jats:sup>18</jats:sup>\n                    F]fluoropenciclovir (FPCV) in C6 rat glioma cells expressing HSV1-sr39tk is increased by a factor of ≈2.0 when compared with C6 cells expressing wild-type HSV1-tk. The increased imaging sensitivity of HSV1-sr39tk when FPCV is used is also demonstrated\n                    <jats:italic>in vivo</jats:italic>\n                    both with tumor cells stably transfected with either HSV1-tk or HSV1-sr39tk, and after hepatic delivery of HSV1-tk or HSV1-sr39tk by using adenoviral vectors. The use of HSV1-sr39tk as a PET reporter gene and FPCV as a PET reporter probe results in significantly enhanced sensitivity for imaging reporter gene expression\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","is_dataset_classified":null,"base_score":6.129050210060545,"endowment":6.129050210060545,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10716999","pmcid":"PMC16007","openalex_id":"https://openalex.org/W1994216715","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA082214","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA82214-01","title":null}],"total_grants":2,"fwci":23.2661,"citation_percentile":0.99747438,"influential_citations":0,"citation_trend":[{"year":2012,"count":21},{"year":2013,"count":16},{"year":2014,"count":11},{"year":2015,"count":7},{"year":2016,"count":5},{"year":2017,"count":13},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":14},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":7},{"year":2026,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.97.6.2785","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.97.6.2785","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10716999","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/16007","host_type":"repository"}],"fields_of_study":["Virus-based gene therapy research","Herpesvirus Infections and Treatments","Neuroblastoma Research and Treatments","Acyclovir","Adenoviridae","Animals","Antiviral Agents","Blotting, Northern","Blotting, Western","Chromatography, High Pressure Liquid","Escherichia coli","Fluorine","Ganciclovir","Genes, Reporter","Herpesvirus 1, Human","Liver","Mice","Mutagenesis","Prodrugs","Rats","Thymidine Kinase","Time Factors","Tomography, Emission-Computed","Transfection","Tumor Cells, Cultured"],"mesh_terms":["Acyclovir","Adenoviridae","Animals","Antiviral Agents","Chromatography, High Pressure Liquid","Escherichia coli","Fluorine","Liver","Prodrugs","Thymidine Kinase","Time Factors","Tomography, Emission-Computed","Transfection","Tumor Cells, Cultured","Blotting, Northern","Blotting, Western","Ganciclovir","Mutagenesis","Genes, Reporter","Herpesvirus 1, Human","Mice","Rats"],"keywords":["Thymidine kinase","Reporter gene","Molecular biology","Transfection","Mutant","Herpes simplex virus","Chemistry","Gene expression","Biology","Gene","Virology","Virus","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T17:04:35.300127Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}