Evidence map›Paper›PMID 26169882›Full record

ArticleNuclear medicine and biology2015

A high-affinity [(18)F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer.

Tanushree Ganguly, Shorouk Dannoon, Mark R Hopkins, Stephanie Murphy, Hendry Cahaya, Joseph E Blecha, Salma Jivan, Christopher R Drake, Cyril Barinka, Ella F Jones and 2 more

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

Article in Nuclear medicine and biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.2field-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

30 citing papers in PubMed, 67 citations in OpenAlex.

  1. Imaging Efficacy of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Trial
  2. Imaging Efficacy of [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Trial
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. A PSMA-targeted doxorubicin small-molecule drug conjugate.Bioorganic & medicinal chemistry letters · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. [Recent progress of positron radionuclide labeled small molecule inhibitors of prostate specific membrane antigen for PET/CT imaging of prostate cancer].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2020
    Review
  17. Theranostics · 2020
    Review
  18. Review
  19. Phase I Study of CTT1057, anJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    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

12 authors at 2 institutions in 2 countries.

Tanushree GangulyDepartment of Chemistry, Washington State University, USA.
Shorouk DannoonDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Mark R HopkinsDepartment of Chemistry, Washington State University, USA.
Stephanie MurphyDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Hendry CahayaDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Joseph E BlechaDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Salma JivanDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Christopher R DrakeDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Cyril BarinkaInstitute of Biotechnology, CR, Prague.
Ella F JonesDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Henry F VanBrocklinDepartment of Radiology and Biomedical Imaging, University of CA, San Francisco, USA.
Clifford E BerkmanDepartment of Chemistry, Washington State University, USA; Cancer Targeted Technology, USA. Electronic address: cberkman@wsu.edu.
Washington State University · USCzech Academy of Sciences, Institute of Biotechnology · CZ

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3M
Probe Optimization for Prostate Cancer DetectionR01CA140617 · NCI · WASHINGTON STATE UNIVERSITY · PI BERKMAN, CLIFFORD · 2010 to 2013
$1.8M
NCI NIH HHS P30 CA016520NCI NIH HHS R01 CA140617
6 · The paper itself

Abstract

introductionIn this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated.

methodsp-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [(18)F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(-) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent.

resultsThe crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [(18)F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(-) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h.

conclusionsWe have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [(18)F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa. ADVANCES IN KNOWLEDGE: The only FDA-approved imaging agent for PCa, Prostascint®, targets PSMA but suffers from inherent shortcomings. The data acquired in this manuscript confirmed that our new generation of [(18)F]-labeled PSMA inhibitor exhibited promising in vivo performance as a PET imaging agent for PCa and is well-positioned for subsequent clinical trials. Implications for Patient Care Our preliminary data demonstrate that this tracer possesses the required imaging characteristics to be sensitive and specific for PCa imaging in patients at all stages of the disease.

Indexed as

Fluorine RadioisotopesAmidesAnimalsAntigens, SurfaceBiological TransportCell Line, TumorDrug StabilityGlutamate Carboxypeptidase IIHumansInhibitory Concentration 50Isotope LabelingMaleMiceModels, MolecularPeptidomimeticsPhosphoric AcidsAmidesAntigens, SurfaceFluorine RadioisotopesFOLH1 protein, humanGlutamate Carboxypeptidase IIPeptidomimeticsphosphoramidic acidPhosphoric AcidsProtease InhibitorsFlourine-18PETPhosphoramidatePSMA

Identifiers

PMID26169882
PMCPMC4624265
OpenAlexW1831395375

What OpenQuestion holds

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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.