Trial reportThe Journal of biological chemistry2012
Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.Science advances · 2024Article
- PET reporter systems for the brain.Trends in neurosciences · 2023Review
- Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy.Molecular therapy oncolytics · 2021Review
- Radionuclide-based molecular imaging allows CAR-T cellular visualization and therapeutic monitoring.Theranostics · 2021Review
- Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide Metabolism.Cell chemical biology · 2020Article
- Imaging CAR T Cell Trafficking with eDHFR as a PET Reporter Gene.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Molecular Imaging with Reporter Genes: Has Its Promise Been Delivered?Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Review
- Review
- Advancing Immune and Cell-Based Therapies Through Imaging.Molecular imaging and biology · 2017Review
- Comparative Analysis of Human Nucleoside Kinase-Based Reporter Systems for PET Imaging.Molecular imaging and biology · 2017Article
- Article
- [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Advances in PET Detection of the Antitumor T Cell Response.Advances in immunology · 2016Review
- Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine.PloS one · 2016Article
- Comparative Analysis of T Cell Imaging with Human Nuclear Reporter Genes.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015Article
- [(18)F]FHBG PET/CT Imaging of CD34-TK75 Transduced Donor T Cells in Relapsed Allogeneic Stem Cell Transplant Patients: Safety and Feasibility.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging.The Journal of clinical investigation · 2015Article
- Applications of in vivo imaging in the evaluation of the pathophysiology of viral and bacterial infections and in development of countermeasures to BSL3/4 pathogens.Molecular imaging and biology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Positron emission tomography (PET) reporter gene imaging can be used to non-invasively monitor cell-based therapies. Therapeutic cells engineered to express a PET reporter gene (PRG) specifically accumulate a PET reporter probe (PRP) and can be detected by PET imaging. Expanding the utility of this technology requires the development of new non-immunogenic PRGs. Here we describe a new PRG-PRP system that employs, as the PRG, a mutated form of human thymidine kinase 2 (TK2) and 2'-deoxy-2'-18F-5-methyl-1-β-L-arabinofuranosyluracil (L-18F-FMAU) as the PRP. We identified L-18F-FMAU as a candidate PRP and determined its biodistribution in mice and humans. Using structure-guided enzyme engineering, we generated a TK2 double mutant (TK2-N93D/L109F) that efficiently phosphorylates L-18F-FMAU. The N93D/L109F TK2 mutant has lower activity for the endogenous nucleosides thymidine and deoxycytidine than wild type TK2, and its ectopic expression in therapeutic cells is not expected to alter nucleotide metabolism. Imaging studies in mice indicate that the sensitivity of the new human TK2-N93D/L109F PRG is comparable with that of a widely used PRG based on the herpes simplex virus 1 thymidine kinase. These findings suggest that the TK2-N93D/L109F/L-18F-FMAU PRG-PRP system warrants further evaluation in preclinical and clinical applications of cell-based therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.