Establishment of a method for predicting bone marrow suppression after I-131 MIBG treatment using flow cytometry

• Project/Area Number: 20K08128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Kanazawa University
• Principal Investigator: WAKABAYASHI HIROSHI 金沢大学, 附属病院, 講師 (60622818)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 放射線 / 核医学 / 被ばく / DNA / フローサイトメトリー / リンパ球 / DNA損傷 / γ-H2AX / リンパ球障害 / 放射線障害 / 核医学治療 / I-131 MIBG治療 / 骨髄抑制 / ドジメトリー

Outline of Research at the Start

I-131 MIBG内用療法は難治性褐色細胞腫、神経芽腫の治療に有用であるが、骨髄抑制が必発である。骨髄抑制のリンパ球障害を顕微鏡目視下で確認する既存方法は煩雑であり、簡易測定法の確立が求められている。本研究では、DNA損傷指標のγ-H2AXとDNA損傷修復指標の53BP1を用いて、治療後のリンパ球障害の程度をフローサイトメトリーで測定する簡易な骨髄抑制予測法の確立を目指す。

Outline of Final Research Achievements

This study aims to establish a simple method for predicting myelosuppression using γ-H2AX, a DNA damage indicator, to measure the degree of lymphocyte damage after radiotherapy by flow cytometry. Lymphocyte damage after external and internal irradiation was evaluated by flow cytometry using γ-H2AX to examine exposure dose, the degree of lymphocyte damage, and changes in lymphocyte damage over time. DNA damage of lymphocytes due to external irradiation was positively correlated with absorbed dose. Recovery from damage caused by external irradiation was observed within 3 days, while lymphocyte damage caused by low-dose internal irradiation was observed to recover within 24 hours. Flow cytometry was an effective method to assess radiation-induced DNA damage quantitatively.

Academic Significance and Societal Importance of the Research Achievements

本研究では、DNA損傷指標のγ-H2AXを用いて、放射線治療後のリンパ球障害の程度をフローサイトメトリーで測定する簡易な骨髄抑制予測法の確立を目指した。フローサイトメトリーで評価できる放射線外照射後のリンパ球障害の程度は線量と相関関係があり、障害の回復過程も確認できた。I-131によるリンパ球障害はフローサイトメトリーでの検出が可能であった。日本の放射線同位元素（RI）治療で用いられる核種は主にI-131であり、本研究の結果は我が国におけるRI治療後の被ばく管理に応用できる。フローサイトメトリーによる評価はRI治療後の被ばく管理に応用でき、広く役立つと考えられる。

Research Products

• [Journal Article] Recent Advances in Radiopharmaceutical Theranostics of Pheochromocytoma and Paraganglioma (2023)
  • Author(s): Xue Zhang , Hiroshi Wakabayashi, Tomo Hiromasa, Daiki Kayano, Seigo Kinuya
  • Journal Title: Semin Nucl Med. Volume: - Issue: 4 Pages: 503-516
  • DOI: 10.1053/j.semnuclmed.2022.12.005
  • Peer Reviewed
• [Journal Article] I-131 metaiodobenzylguanidine therapy is a significant treatment option for pheochromocytoma and paraganglioma (2022)
  • Author(s): Zhang X, Wakabayashi H, Kayano D, Inaki A, Kinuya S
  • Journal Title: Nuklearmedizin Volume: 61 Issue: 03 Pages: 231-239
  • DOI: 10.1055/a-1759-2050
  • Peer Reviewed
• [Journal Article] High-dose 131I-mIBG as consolidation therapy in pediatric patients with relapsed neuroblastoma and ganglioneuroblastoma: the Japanese experience (2020)
  • Author(s): Wakabayashi Hiroshi、Kayano Daiki、Inaki Anri、Araki Raita、Kuroda Rie、Ikawa Yasuhiro、Fujiki Toshihiro、Akatani Norihito、Yamase Takafumi、Watanabe Satoru、Hiromasa Tomo、Kunita Yuji、Mori Hiroshi、Saito Shintaro、Nishimura Ryosei、Wada Taizo、Kinuya Seigo
  • Journal Title: Annals of Nuclear Medicine Volume: 34 Issue: 11 Pages: 840-846
  • DOI: 10.1007/s12149-020-01514-2
  • Peer Reviewed
• [Journal Article] High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan. (2020)
  • Author(s): Kayano D, Wakabayashi H, Nakajima K, Kuroda R, Watanabe S, Inaki A, Toratani A, Akatani N, Yamase T, Kunita Y, Hiromasa T, Takata A, Mori H, Saito S, Araki R, Taki J, Kinuya S
  • Journal Title: Ann Nucl Med Volume: 34 Issue: 6 Pages: 397-406
  • DOI: 10.1007/s12149-020-01460-z
  • Peer Reviewed
• [Journal Article] Radiation exposure in nurses during care of 131I-MIBG therapy for pediatric patients with high-risk neuroblastoma (2020)
  • Author(s): Taniguchi Yuka、Wakabayashi Hiroshi、Inaki Anri、Kayano Daiki、Yamada Masako、Kinuya Seigo
  • Journal Title: Annals of Nuclear Medicine Volume: 34 Issue: 6 Pages: 441-447
  • DOI: 10.1007/s12149-020-01466-7
  • Peer Reviewed
• [Presentation] The Process of Radiation Exposure Lymphocyte Damage Assessed by γH2AX Expression Level using Flow Cytometry. (2022)
  • Author(s): Chen Z, Wakabayashi H, Kuroda R, Kitamura Y, Kozaka T, Saito S, Inaki A, Kayano D, Kinuya S.
  • Organizer: 35th of Annual congress of the European society of nuclear medicine
• [Presentation] 177Lu-DOTATATEシンチグラフィによる標的臓器体積測定：CTとの比較. (2022)
  • Author(s): 張 雪, 小西貴広, 若林大志, 米山寛人, 稲木杏吏, 廣正 智, 渡辺 悟, 森 博史, 赤谷憲一, 山瀬喬史, 國田優志, 齊藤晋太郎, 萱野大樹, 絹谷清剛.
  • Organizer: 第50回断層映像研究会
• [Presentation] Personalized dosimetry of kidney in patients undergoing therapy with 177Lu-DOTATATE. (2022)
  • Author(s): 張 雪, 小西貴広, 若林大志, 米山寛人, 稲木杏吏, 廣正 智, 渡辺 悟, 森 博史, 赤谷憲一, 山瀬喬史, 國田優志, 齊藤晋太郎, 萱野大樹, 絹谷清剛.
  • Organizer: 第3回標的アイソトープ治療線量評価研究会