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2021 Fiscal Year Research-status Report

Breast cancer tumors in deep tissue imaging with bi-modal NIR/MRI probe

Research Project

Project/Area Number 21K15577
Research InstitutionTokyo University of Science

Principal Investigator

ドアン テイキンユン  東京理科大学, 研究推進機構生命医科学研究所, 助教 (70838870)

Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsOTN-NIR / MRI / multimodal imaging / breast cancer / herceptin / Her 2
Outline of Annual Research Achievements

The bimodal OTN-NIR and MR imaging probe has been successfully developed. The probe is composed of GdDOTA conjugated to polymeric micelles at different ratios and locations. The fluorescence and T1 contrast enhancement effect were investigated in various media to evaluate the stability and effectiveness of the probe. The probe shows and stable fluorescence during the interaction with plasma proteins and exhibited an excellent relaxivity up to 6 folds compared to GdDOTA. The probe was applied to image the mouse using two techniques. The images show that the probe is well bright to depict the blood vessel and margin the organ during circulation. The probe can elongate the circulation and evade from the capturing by macrophage. Herceptin bound on the surface showed the good binding affinity.

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

The developed bimodal organic probe exhibits a cohesive and stable manners in biological environment. These behaviors are important for the probe circulating inside the body where multiple environment changes such as pH, tonicity, diluted concentration, or plasma protein interaction can damage the structure and reduce the imaging effectiveness. The cohesion and stability of the probe can be obtained by regulating the Gd-DOTA ratios and locations, i.e., at the core border, the structure is solidified, and the bimodal properties are preserved. Moreover, the solidified probe showed an excellent T1 contrast enhancement in MRI, along with an elongating blood circulation.
The conjugating with Herceptin confirmed the presence of antibody with a high efficient binding affinity.

Strategy for Future Research Activity

1. Assessment for targeting efficiency in vitro will use two kinds of cells including SKBR 3 overexpressing of Her 2 antigen and MCF 7 low expressing of Her-2 antigen. The dependence of targeting efficiency on the structural diameters and, temperature-, dose- and time- dependence will be obtained by flow cytometry and immunofluorescence.
2. Determine the cytotoxic effect of the probe will use SKBR 3, MCF 7 to evaluate the proliferation and viabilities. The dose-dependence toxicity will be evaluated by flow cytometry and immunofluorescence.

Causes of Carryover

The budget will be paid for the materials and reagents that necessary for the experiments.
Moreover, the budget will also use for some small tools that need for the samples characterization and data analysis, as well as the equipment rental fee.
Besides, the amount will be used to pay for the service relating to paper submission such as English proofing, submission fee.
At last, the budget will be used to pay for the member fee and conference fee that the principal investigator will attend in the next fiscal years.

  • Research Products

    (7 results)

All 2022 2021

All Journal Article (2 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Book (1 results) Funded Workshop (1 results)

  • [Journal Article] The influence of Gd-DOTA conjugating ratios to PLGA-PEG micelles encapsulated IR-1061 on bimodal over-1000 nm near-infrared fluorescence and magnetic resonance imaging2022

    • Author(s)
      Doan Thi Kim Dung、Umezawa Masakazu、Ohnuki Kazunobu、Nigoghossian Karina、Okubo Kyohei、Kamimura Masao、Yamaguchi Masayuki、Fujii Hirofumi、Soga Kohei
    • Journal Title

      Biomaterials Science

      Volume: 10 Pages: 1217~1230

    • DOI

      10.1039/d1bm01574e

  • [Journal Article] Influence of Physiological Media on over-1000 nm NIR Fluorescent DSPE-PEG Micelles for Bio-imaging2022

    • Author(s)
      Doan Thi Kim Dung、Umezawa Masakazu、Kobayashi Hisanori、Oshima Atsushi、Ikeda Kazuno、Okubo Kyohei、Kamimura Masao、Soga Kohei
    • Journal Title

      Chemistry Letters

      Volume: 51 Pages: 208~211

    • DOI

      10.1246/cl.210700

  • [Presentation] Developing of dual modal OTN-NIR/MRI imaging probe for intraoperative breast cancer imaging2021

    • Author(s)
      Doan Thi Kim Dung, Hirofumi Fujii
    • Organizer
      The 29th Annual Meeting of the Japanese Breast Cancer Society
    • Int'l Joint Research
  • [Presentation] Rare-Earth Doped Ceramics for Near Infrared Bio and Medical Photonics2021

    • Author(s)
      Kohei Soga, Kyohei Okubo, Masakazu Umezawa, Doan Thi Kim Dung, Masao Kamimura
    • Organizer
      14th Pacific Rim Conference on Ceramic and Glass Technology (PACRIM 14), Dec 13-16, 2021
    • Int'l Joint Research
  • [Presentation] Materials Design and Applications of the Near Infrared Fluorescent Agents for Biological and Medical Uses2021

    • Author(s)
      Kohei Soga, Kyohei Okubo, Masakazu Umezawa, Thi Kim Dung Doan, Karina Nigoghossian, Masao Kamimura
    • Organizer
      THERMEC 2021 Virtual Conference, Jun 1-5, 2021
    • Int'l Joint Research
  • [Book] Multimodal Imaging with NIR Light2021

    • Author(s)
      Thi Kim Dung Doan
    • Total Pages
      223-263
    • Publisher
      Springer Singapore
    • ISBN
      978-981-15-9627-8
  • [Funded Workshop] The 29th Annual Meeting of the Japanese Breast Cancer Society2021

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Published: 2022-12-28  

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