• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Potential mechanism of Gadolinium penetration via intact blood-brain barriers and the effect of Gd retention to brain cancer proliferation

Research Project

Project/Area Number 19K17224
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionGunma University

Principal Investigator

Kartamihardja Achmad  群馬大学, 大学院医学系研究科, 助教 (70806439)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsGadolinium / GBCA / Gadolinium retention / GDD / NSF / choroid plexus / contrast agents / Transmetallation / Gadolinium deposition / neutrophil elastase / astroglioma / meduloblastoma / Contrast agents (GBCA) / Fe(II) / Purkinje cells / Gadolinium toxicity / Gadolinium distribution / Blood-brain barrier
Outline of Research at the Start

Previous studies showed that Gd retention may occur in the brain tissue of normal patients. The mechanism of how Gd can penetrate the brain barrier resulting in retention in the brain tissue is yet to be elucidated. Unchelated Gd at low concentration has been shown to increase cell proliferation, but these phenomenon on brain tumor cells is unknown.
In this research proposal, our aims are 1) To investigate the mechanism of Gd retention in the brain tissue by in vivo and in vitro studies, and 2) To investigate the effect of GBCAs exposure on the brain cancer cell lines by in vitro analysis.

Outline of Final Research Achievements

We found no significant differences in Gd concentration when Gadolinium-based contrast agents (GBCA) were incubated with transferrin. Incubation with Fe(II) did not cause any changes to the Purkinje cell arborization compared the control neurons. Fe(II) increased the effect of gadopentetate to the dendrite arborization, but it did not increase the effect of gadobutrol.
Fibrotic markers were increased in the skin on renal failure mouse model that was injected with gadodiamide, while only collagen 1α and TGF-β mRNA expression were higher in the gadopentetate group. NE activity in the blood serum and the expression of skin NE was significantly higher in the GBCA-treated mice compared to the control. We investigated the GBCA effect on the C6-astroglioma and TE761-medulloblastoma in-vitro. GBCAs significantly increase the C6 proliferation, but the effect was less significant in TE761 cells.

Academic Significance and Societal Importance of the Research Achievements

This project provides the information of:
The effect of Gd to the Purkinje cells, provide a background to reveal the mechanism of Gd retention in the brain, involvement of NE Skin lesion development in the Nephrogenic systemic fibrosis, and the effect of Gd to the proliferation of cancer cell lines.

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (6 results)

All 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Quantitative analysis of Gd in the protein content of the brain following single injection of gadolinium-based contrast agents (GBCAs) by size exclusion chromatography2019

    • Author(s)
      Kartamihardja AAP, Hanaoka F, Andriana P, Kameo S, Takahashi A, Koyama H, Tsushima Y.
    • Journal Title

      BJR

      Volume: 印刷中 Issue: 1099 Pages: 20190062-20190062

    • DOI

      10.1259/bjr.20190062

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The extra miles on preventing nephrogenic systemic fibrosis2019

    • Author(s)
      Achmad Adhipatria Perayabangsa Kartamihardja and Yoshito Tsushima
    • Journal Title

      Quantitative Imaging in Medicine and Surgery

      Volume: 9 Issue: 11 Pages: 1911-1913

    • DOI

      10.21037/qims.2019.09.17

    • Related Report
      2019 Research-status Report
    • Open Access
  • [Journal Article] Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer2019

    • Author(s)
      Yamaguchi A, Achmad A, Hanaoka H, Heryanto YD, Bhattarai A, Ratianto, Khongorzul E, Shintawati R, Kartamihardja AAP, Kanai A, Sugo Y, S Ishioka N, Tetsuya H, Tsushima Y
    • Journal Title

      BMC Cancer

      Volume: 19 Issue: 1 Pages: 1-8

    • DOI

      10.1186/s12885-019-6238-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Changes in the Purkinje cell’s synaptic density post-incubation of gadobutrol and ferrous ion: an in-vitro study2020

    • Author(s)
      Achmad Adhipatria Perayabangsa Kartamihardja
    • Organizer
      Japan Radiology Conference 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Changes in the purkinje cell's synaptic density after GBCA exposure: an in-vitro study2019

    • Author(s)
      Achmad Adhipatria Perayabangsa Kartamihardja
    • Organizer
      Japan Radiology Conference
    • Related Report
      2019 Research-status Report
  • [Presentation] Quantitative analysis of gadolinium in the protein content of the brain post-administration of gadopentetate2019

    • Author(s)
      Achmad Adhipatria Perayabangsa Kartamihardja
    • Organizer
      Japan Radiology Conference
    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi