Evidence map›Paper›PMID 27035974›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

Woosuk Kim, Thuc M Le, Liu Wei, Soumya Poddar, Jimmy Bazzy, Xuemeng Wang, Nhu T Uong, Evan R Abt, Joseph R Capri, Wayne R Austin and 18 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 86 citations in OpenAlex.

  1. Challenges in tracer development for tumor microenvironment (TME) imaging.European journal of nuclear medicine and molecular imaging · 2026
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  3. Can Nuclear Imaging Detect Trained Immunity in Cardiovascular Disease?Arteriosclerosis, thrombosis, and vascular biology · 2026
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  5. Advancing In Vivo Detection of T-Cell Function: Development and Preclinical Evaluation ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
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  8. [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
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  9. [Communications biology · 2024
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  10. Immune checkpoint inhibition: a future guided by radiology.The British journal of radiology · 2023
    Review
  11. Fluorinated carbohydrates forChemical Society reviews · 2023
    Review
  12. Article
  13. An improved radiosynthesis of [Journal of labelled compounds & radiopharmaceuticals · 2022
    Article
  14. Review
  15. Article
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  17. Review
  18. Review
  19. Article
  20. Review
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

28 authors at 6 institutions in 1 country.

Woosuk KimDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Thuc M LeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Liu WeiDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Soumya PoddarDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Jimmy BazzyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Xuemeng WangDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Nhu T UongDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Evan R AbtDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Joseph R CapriDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Wayne R AustinAbcam, Cambridge, MA 02139-1517;
Juno S Van ValkenburghAhmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095;
Dalton SteeleAhmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095;
Raymond M GipsonDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095;
Roger SlavikDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Anthony E CabebeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Thotsophon TaechariyakulDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Shahriar S YaghoubiCellSight Technologies, Inc., San Francisco, CA 94107;
Jason T LeeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Crump Institute for Molecular Imaging, University of California, Los Angeles, CA 90095;
Saman SadeghiDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Arnon LavieDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607;
Kym F FaullDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; The Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095;
Owen N WitteDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Department of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095;
Timothy R DonahueDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
Michael E PhelpsDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Crump Institute for Molecular Imaging, University of California, Los Angeles, CA 90095; cradu@mednet.ucla.edu mphelps@mednet.ucla.edu.
Harvey R HerschmanDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Ken HerrmannDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Johannes CzerninDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095;
Caius G RaduDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Ahmanson Translational Imaging Division, University of California, Los Angeles, CA 90095; cradu@mednet.ucla.edu mphelps@mednet.ucla.edu.
University of California, Los Angeles · USAbcam (United States) · USBroad Center · USCellSight Technologies (United States) · USSalk Institute for Biological Studies · USUniversity of Illinois Chicago · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Transductionally Redirected /Transcriptionally RestricteP50CA086306 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HERSCHMAN, HARVEY R. · 2000 to 2014
$29.0M
UCLA Scholars in Oncologic Molecular lmaging (SOMI)R25CA098010 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PHELPS, MICHAEL E · 2003 to 2013
$5.0M
PET Imaging-guided Personalized Therapy in Pancreatic CancerR01CA187678 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CZERNIN, JOHANNES, DONAHUE, TIMOTHY R · 2014 to 2018
$2.8M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA086306NCI NIH HHS R01 CA187678NCI NIH HHS R25 CA098010
6 · The paper itself

Abstract

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

Indexed as

Adenine NucleotidesAnimalsAntineoplastic AgentsArabinonucleosidesBiomarkers, TumorCell Line, TumorClofarabineContrast MediaDeoxycytidine KinaseHumansLeukemiaMiceNeoplasmsPositron-Emission TomographyProdrugsRatsAdenine NucleotidesAntineoplastic AgentsArabinonucleosidesBiomarkers, TumorClofarabineContrast MediaDeoxycytidine KinaseProdrugscancerdeoxycytidine kinasenucleotide metabolismPET imaging

Identifiers

PMID27035974
PMCPMC4839461
OpenAlexW2322439273

What OpenQuestion holds

Textmetadata
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.