Evidence map›Paper›PMID 20810757›Full record

ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2010

A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase suitable for PET during treatment with acycloguanosine-based cytotoxic drugs.

Yury Likar, Juan Zurita, Konstantin Dobrenkov, Larissa Shenker, Shangde Cai, Anton Neschadim, Jeffrey A Medin, Michel Sadelain, Hedvig Hricak, Vladimir Ponomarev

Open access · bronzeAbstract read
In one paragraph

Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 61 citations in OpenAlex.

  1. Trial
  2. A Genetically Engineered Reporter System Designed forJournal of the American Chemical Society · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Molecular therapy oncolytics · 2021
    Review
  13. Article
  14. Non-invasive Reporter Gene Imaging of Cell Therapies, including T Cells and Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Review
  15. Frontiers in immunology · 2020
    Review
  16. Article
  17. How Non-invasiveFrontiers in physiology · 2020
    Review
  18. Molecular Imaging with Reporter Genes: Has Its Promise Been Delivered?Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Review
  19. Review
  20. Imaging of CAR T-Cells in Cancer Patients: Paving the Way to Treatment Monitoring and Outcome Prediction.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Yury LikarDepartment of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Juan Zurita
Konstantin Dobrenkov
Larissa Shenker
Shangde Cai
Anton Neschadim
Jeffrey A Medin
Michel Sadelain
Hedvig Hricak
Vladimir Ponomarev
Memorial Sloan Kettering Cancer Center · USUniversity Health Network · CAUniversity of Toronto · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Tumor Evolution and Changes in MetabolismP50CA086438 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI RIVIERI, ISABELLE · 2000 to 2015
$29.9M
Memorial Sloan Kettering Small Animal Imaging ResearchR24CA083084 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI KOUTCHER, JASON ARTHUR · 1999 to 2006
$4.4M
PET Imaging of Tumor Targeting &Role of T LymphocytesR01CA102352 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PONOMAREV, VLADIMIR · 2005 to 2008
$1.3M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA08748NCI NIH HHS P50 CA086438NCI NIH HHS P50 CA86438-01NCI NIH HHS R01 CA102352NCI NIH HHS R24 CA083084NCI NIH HHS R24 CA83084
6 · The paper itself

Abstract

unlabelledIn this article, we describe a series of new human-derived reporter genes based on human deoxycytidine kinase (dCK) suitable for clinical PET.

methodsNative dCK and its mutant reporter genes were tested in vitro and in vivo for their phosphorylation of pyrimidine- and acycloguanosine-based radiotracers including 2'-deoxy-2'-fluoroarabinofuranosylcytosine, 2'-fluoro-2'-deoxyarabinofuranosyl-5-ethyluracil (FEAU), penciclovir, and 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine (FHBG) and clinically applied antiviral and anticancer drugs.

resultsCells transduced with dCK mutant reporter genes showed high in vitro and in vivo uptake of pyrimidine-based radiopharmaceuticals ((18)F-FEAU) comparable to that of herpes simplex virus type-1 thymidine kinase (HSV1-tk)-transduced cells. These mutants did not phosphorylate acycloguanosine-based radiotracers ((18)F-FHBG) or antiviral drugs (ganciclovir). Furthermore, the mutants displayed suicidal activation of clinically used pyrimidine-based prodrugs (cytarabine, gemcitabine).

conclusionThe mutants of human dCK can be used as pyrimidine-specific PET reporter genes for imaging with (18)F-FEAU during treatment with acycloguanosine-based antiviral drugs. Additionally, the prosuicidal activity of these reporters with pyrimidine-based analogs will allow for the safe elimination of transduced cells.

Indexed as

MutationPositron-Emission TomographyAcyclovirAnimalsAntineoplastic AgentsArabinofuranosyluracilCell Line, TumorDeoxycytidine KinaseFluorine RadioisotopesGenes, ReporterHumansLymphocytesMiceNIH 3T3 CellsPhosphorylationProdrugs2'-fluoro-5-ethylarabinosyluracilAcyclovirAntineoplastic AgentsArabinofuranosyluracilDeoxycytidine KinaseFluorine RadioisotopesProdrugsRadioactive Tracers

Identifiers

PMID20810757
PMCPMC4405132
OpenAlexW2160438188

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.