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Sentinel lymph node metastasis imaging by using nanoparticle carriers in an animal study

Research Project

Project/Area Number 21592565
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe Nippon Dental University

Principal Investigator

TSUCHIMOCHI Makoto  日本歯科大学, 新潟生命歯学部, 教授 (20095186)

Co-Investigator(Renkei-kenkyūsha) TSUBOKAWA Norio  新潟大学, 自然科学系, 教授 (20018675)
HAYAMA Kazuhide  日本歯科大学, 新潟生命歯学部, 准教授 (60120713)
KAMETA Ayako  日本歯科大学, 新潟生命歯学部, 講師 (00328866)
SUE Mikiko  日本歯科大学, 新潟生命歯学部, 助教 (60339471)
Research Collaborator SASAGAWA Ichiro  日本歯科大学, 新潟生命歯学部, 教授 (00095134)
YOSHIE Sumio  日本歯科大学, 新潟生命歯学部, 教授 (30095278)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsRI / センチネルリンパ節 / ナノ粒子 / 複合イメージング / 近赤外蛍光 / 分子イメージング / センチネルリンパ節生検
Research Abstract

We propose a new approach using multimodality imaging to facilitate sentinel node biopsy examinations, in which radioactive and near infrared(NIR) fluorescent nanoparticles can depict deep situated sentinel nodes and fluorescent nodes, as well as simultaneously visualize anatomical configurations in the field of interest. For this reason we have developed polyamidoamine(PAMAM) coated silica nanoparticles loaded with technetium-99m(Tc-99m) and ICG. To test the feasibility and utility of this dual-modality imaging system we conducted animal studies. The mean diameter of PAMAM coated silica nanoparticles was 30-50 nm as evaluated by images of transmission electron microscopy and scanning electron microscopy. The distribution of the particle size was measured by a laser scattering particle size analyzer(SALD-7100, Shimadzu, Japan). The peak of the distribution was 30 nm in ethanol solution. The combined labeling with both Tc-99m and ICG-Sulfo-OSu was verified by thin layer chromatography, … More TLC, before each experiment. 0.1 ml of the nanoparticle solution(7.4 MBq, except for one rat ; with 3.7 MBq, and 1 micro-gramm ICG) was submucosally injected in the tongue of six male Wister rats. Lymphoscintigraphy(sequential static images, every 5 minutes) was performed for 6 rats for one hour immediately after injection. Scintigraphic images showed an increased accumulation of Tc-99m in the neck with a markedly increased uptake at the injection site. Single increased nodal uptake was seen in 4 of 6 rats in the final static images. After completion of lymphoscintigraphy, animals were euthanized. As skin incision was made and 19 lymph nodes were identified in the dissected necks of 6 rats. After lymph node excision, contact-radiography was performed which revealed 3 markedly increased uptake nodes and 3 weak uptake nodes. NIR fluorescence imaging was performed on all dissected necks. The PDE system(Hamamatsu Photonics Co, Japan) provided clear fluorescence images of lymph nodes in the neck with anatomical configurations real time. The intensity of fluorescence was arbitrarily evaluated and 6 lymph nodes were weak to strong, (+)~(+++), and other lymph nodes were evaluated as having no fluorescence. Increased radioactive nodes coincided with fluorescent nodes. Radioactivity of 15 excised lymph nodes in 4 rats was assayed with a gamma-well counter. The radioactivity comparison revealed a large difference between the high fluorescence intensity group(4 lymph nodes, mean%; 0.109±0.067) and thelow or no fluorescence intensity group(8 lymph nodes, mean%; 0.001±0.000), (p<0.05). TEM revealed that small black granules were localized and dispersed within the cytoplasm of macrophages in lymph nodes. The appearance of small sphericalgranules was restricted to macrophages but not other lymphatic cells. Although further studies are needed to determine the appropriate sensitivity and safety of thisdual imaging nanoparticles, the results may promise for a better target nodes detection by the dual modality method in sentinel node biopsy. Less

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (15 results)

All 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (12 results) Remarks (1 results)

  • [Journal Article] Intraoperative gamma cameras for radioguided surgery : Technical characteristics, performance parameters, and clinical applications2012

    • Author(s)
      Tsuchimochi M, Hayama K.
    • Journal Title

      Phys Med.

      Volume: 29 Issue: 2 Pages: 126-138

    • DOI

      10.1016/j.ejmp.2012.05.002

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intraoperative gamma cameras for radioguided surgery : Technical characteristics, performance parameters, and clinical applications

    • Author(s)
      Tsuchimochi M, Hayama K
    • Journal Title

      European Journal of Medical Physics

      Volume: (accept)(平成24年5月にDOI決定)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Dual-modality Imaging Using Radionuclide and Near-infrared Fluorescence Nanoparticles for Sentinel Lymph Node Biopsy : An Animal Study2011

    • Author(s)
      Tsuchimochi M, Hayama K, Kameta A, Yamaguchi H, Toyama M, Sasagawa I, Tsubokawa N
    • Organizer
      2011 World Molecular Imaging Congress
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2011-09-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Dual-modality Imaging Using Radionuclide and Near-infrared Fluorescence Nanoparticles for Sentinel Lymph Node Biopsy : An Animal Study2011

    • Author(s)
      Tsuchimochi; K.Hayama; A.Kameta; H.Yamaguchi; M.Toyama; I.Sasagawa; N.Tsubokawa
    • Organizer
      2011 World Molecular Imaging Congress
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2011-09-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 小型半導体ガンマカメラと複合イメージングプローブを用いたセンチネルリンパ節生検の可能性2011

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, 外山三智雄, 笹川一郎, 坪川紀夫
    • Organizer
      第65回日本口腔科学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-21
    • Related Report
      2011 Final Research Report
  • [Presentation] 小型半導体ガンマカメラと複合イメージングプローブを用いたセンチネルリンパ節生検の可能性2011

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, 外山三智雄, 笹川一郎, 坪川紀夫
    • Organizer
      第65回NPO法人日本口腔科学会学術集会
    • Place of Presentation
      東京都江戸川区タワーホール船堀
    • Year and Date
      2011-04-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 核医学と近赤外蛍光の複合イメージングナノ粒子によるセンチネルリンパ節生検の可能性2011

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子
    • Organizer
      第29回日本口腔腫瘍学会総会・学術大会
    • Place of Presentation
      熊本市崇城大学市民ホール
    • Year and Date
      2011-01-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 核医学と近赤外蛍光の複合イメージングナノ粒子によるセンチネルリンパ節生検の可能性2011

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, 諏江美樹子
    • Organizer
      第29回日本口腔腫瘍学会総会・学術大会
    • Place of Presentation
      熊本
    • Year and Date
      2011-01-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Sentinel node imaging of radioactive and near infrared fluorescent nanocarriers2010

    • Author(s)
      Tsuchimochi M, Hayama K, Kameta A, Toyama M, Sasagawa I, TsubokawaN
    • Organizer
      The 7th International Sentinel Node Society Meeting
    • Place of Presentation
      横浜
    • Year and Date
      2010-11-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Sentinel node imaging of radioactive and near infrared fluorescent nanocarriers ; an animal study2010

    • Author(s)
      Tsuchimochi, Hayama, Tsubokawa, et al.
    • Organizer
      ISNS 2010, The 7^<th> International Sentinel Node Society Meeting
    • Place of Presentation
      パシフィコ横浜会議センター
    • Year and Date
      2010-11-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 99mTcと近赤外蛍光のdualイメージングナノ粒子キャリアによるセンチネルリンパ節生検の試み2010

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, 外山三智雄, 笹川一郎, 坪川紀夫
    • Organizer
      第12回Sentinel Node Navigation Surgery研究会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] ナノ粒子を用いた^<99m>Tcと近赤外蛍光の複合イメージングによるセンチネルリンパ節生検の可能性2010

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, ら
    • Organizer
      第50回日本核医学会学術総会
    • Place of Presentation
      埼玉市大宮ソニックシティ
    • Year and Date
      2010-11-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] 歯科領域の核医学,小型半導体ガンマカメラによるセンチネルリンパ節バイオプシー2010

    • Author(s)
      土持眞
    • Organizer
      第857回放射線診療研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-09-13
    • Related Report
      2011 Final Research Report
  • [Presentation] ナノ粒子を用いた99mTcと近赤外蛍光の複合イメージングによるセンチネルリンパ節生検の可能性2010

    • Author(s)
      土持眞, 羽山和秀, 亀田綾子, 外山三智雄, 笹川一郎, 坪川紀夫
    • Organizer
      第50回日本核医学会学術総会
    • Place of Presentation
      大宮
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.ngt.ndu.ac.jp/guide/kouza/dental12.html

    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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