Evidence map›Paper›PMID 24639459›Full record

ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2014

Reduced 64Cu uptake and tumor growth inhibition by knockdown of human copper transporter 1 in xenograft mouse model of prostate cancer.

Huawei Cai, Jiu-sheng Wu, Otto Muzik, Jer-Tsong Hsieh, Robert J Lee, Fangyu Peng

Abstract read
In one paragraph

Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Preclinical Theranostic Profiling of [Molecules (Basel, Switzerland) · 2025
    Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Nuclear Medicine and Cancer Theragnostics: Basic Concepts.Diagnostics (Basel, Switzerland) · 2023
    Review
  11. Review
  12. Editorial:Frontiers in medicine · 2023
    Article
  13. Review
  14. Review
  15. Recent Advances in Cancer Imaging withNuclear medicine and molecular imaging · 2022
    Review
  16. Review
  17. Article
  18. Review
  19. EJNMMI research · 2019
    Article
  20. Radiobiological Characterization ofMolecules (Basel, Switzerland) · 2018
    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

6 authors.

Huawei CaiDepartment of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.
Jiu-sheng Wu
Otto Muzik
Jer-Tsong Hsieh
Robert J Lee
Fangyu Peng

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
RESEARCH RESOURCE IN RADIONUCLIDE RESEARCHR24CA086307 · NCI · WASHINGTON UNIVERSITY · PI WELCH, MICHAEL J. · 1999 to 2009
$8.4M
Human Copper Transporter 1 as Reporter Gene for ImagingR21EB005331 · NIBIB · WAYNE STATE UNIVERSITY · PI PENG, FANGYU · 2007 to 2008
$375k
NCI NIH HHS P30 CA142543NCI NIH HHS R24 CA086307NCI NIH HHS R24 CA86307NIBIB NIH HHS R21 EB005331NIBIB NIH HHS R21EB005331-01A2
6 · The paper itself

Abstract

unlabelledCopper is an element required for cell proliferation and angiogenesis. Human prostate cancer xenografts with increased (64)Cu radioactivity were visualized previously by PET using (64)CuCl2 as a radiotracer ((64)CuCl2 PET). This study aimed to determine whether the increased tumor (64)Cu radioactivity was due to increased cellular uptake of (64)Cu mediated by human copper transporter 1 (hCtr1) or simply due to nonspecific binding of ionic (64)CuCl2 to tumor tissue. In addition, the functional role of hCtr1 in proliferation of prostate cancer cells and tumor growth was also assessed.

methodsA lentiviral vector encoding short-hairpin RNA specific for hCtr1 (Lenti-hCtr1-shRNA) was constructed for RNA interference-mediated knockdown of hCtr1 expression in prostate cancer cells. The degree of hCtr1 knockdown was determined by Western blot, and the effect of hCtr1 knockdown on copper uptake and proliferation were examined in vitro by cellular (64)Cu uptake and cell proliferation assays. The effects of hCtr1 knockdown on tumor uptake of (64)Cu were determined by PET quantification and tissue radioactivity assay. The effects of hCtr1 knockdown on tumor growth were assessed by PET/CT and tumor size measurement with a caliper.

resultsRNA interference-mediated knockdown of hCtr1 was associated with the reduced cellular uptake of (64)Cu and the suppression of prostate cancer cell proliferation in vitro. At 24 h after intravenous injection of the tracer (64)CuCl2, the (64)Cu uptake by the tumors with knockdown of hCtr1 (4.02 ± 0.31 percentage injected dose per gram [%ID/g] in Lenti-hCtr1-shRNA-PC-3 and 2.30 ± 0.59 %ID/g in Lenti-hCtr1-shRNA-DU-145) was significantly lower than the (64)Cu uptake by the control tumors without knockdown of hCtr1 (7.21 ± 1.48 %ID/g in Lenti-SCR-shRNA-PC-3 and 5.57 ± 1.20 %ID/g in Lenti-SCR-shRNA-DU-145, P < 0.001) by PET quantification. Moreover, the volumes of prostate cancer xenograft tumors with knockdown of hCtr1 (179 ± 111 mm(3) for Lenti-hCtr1-shRNA-PC-3 or 39 ± 22 mm(3) for Lenti-hCtr1-shRNA-DU-145) were significantly smaller than those without knockdown of hCtr1 (536 ± 191 mm(3) for Lenti- SCR-shRNA-PC-3 or 208 ± 104 mm(3) for Lenti-SCR-shRNA-DU-145, P < 0.01).

conclusionOverall, data indicated that hCtr1 is a promising theranostic target, which can be further developed for metabolic imaging of prostate cancer using (64)CuCl2 PET/CT and personalized cancer therapy targeting copper metabolism.

Indexed as

AnimalsBlotting, WesternCation Transport ProteinsCell Line, TumorCell ProliferationCopperCopper RadioisotopesCopper Transporter 1Genetic VectorsHumansLentivirusMaleMicePositron-Emission TomographyProstatic NeoplasmsRadiopharmaceuticalsCation Transport ProteinsCopperCopper RadioisotopesCopper Transporter 1cupric chlorideRadiopharmaceuticalsRNA, Small Interfering64Cu-chloridecopper metabolismhuman copper transporter 1PET/CTprostate cancer

Identifiers

PMID24639459
PMCPMC4600613

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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.