標識抗体を利用したがんの診断と治療

• Project/Area Number: 12217021
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Gunma University
• Principal Investigator: 遠藤 啓吾 群馬大学, 大学院・医学系研究科, 教授 (10115800)
• Co-Investigator(Kenkyū-buntansha): 織内 昇 群馬大学, 大学院・医学系研究科, 助教授 (40292586) ; 井上 登美夫 横浜市立大学, 医学研究科, 教授 (80134295) ; 荒野 泰 千葉大学, 薬学研究院, 教授 (90151167) ; 飯田 靖彦 群馬大学, 大学院・医学系研究科, 助教授 (60252425) ; 青木 純 群馬大学, 医学部, 助教授 (80212364)
• Project Period (FY): 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥48,800,000 (Direct Cost: ¥48,800,000); Fiscal Year 2004: ¥10,600,000 (Direct Cost: ¥10,600,000); Fiscal Year 2003: ¥9,500,000 (Direct Cost: ¥9,500,000); Fiscal Year 2002: ¥9,000,000 (Direct Cost: ¥9,000,000); Fiscal Year 2001: ¥10,200,000 (Direct Cost: ¥10,200,000); Fiscal Year 2000: ¥9,500,000 (Direct Cost: ¥9,500,000)
• Keywords: 放射線 / 免疫学 / 抗体 / 癌 / 遺伝子 / イットリウム-90 / 放射性同位元素 / PET / 胃癌 / FAMT / 放射性ヨード-131 / 悪性リンパ腫 / 放射性ヨード / モノクローナル抗体 / リポソーム / 胃がん / がん治療 / 放射免疫療法 / 核医学治療

Research Abstract

モノクローナル抗体は対応する抗原と特異的に結合するが、放射性同位元素(アイソトープ;RI)で標識した抗体もまた抗原と特異的に結合し病巣に集積する。この性質を利用してRI標識抗体は副作用の少ない腫瘍特異的な治療法として臨床応用できると期待されている。抗体の標識に用いる治療用RIとしては、放射性ヨード(I)-131とイットリウム(Y)-90を用いて悪性リンパ腫を対象にB細胞表面抗原CD20に対するモノクローナル抗体を用いて検討した。イットリウム(Y)-90とDTPA結合抗CD20抗体は単に混和するのみで、DTPAを介してY-90標識され生体内でも安定していた。またY-90標識抗CD20抗体を投与したところ悪性リンパ腫患者で腫瘍の消失、縮小効果が確認された。Y-90と抗体との結合にDTPA以外のキレート剤DOTAを用いたDOTA結合抗体とも標識することができた。悪性リンパ腫以外の悪性腫瘍に応用すべく、担がんヌードマウス、放射性ヨード標識抗体を用いて新規モノクローナル抗体を検索している。
ポジトロン断層撮影(PET)を用いる検査及び拡散強調MRI画像がこれらの治療効果の判定に役立つことを明らかにした。Y-90標識抗CD20抗体による治療でもブドウ糖誘導体FDGを用いるPET検査でその治療効果を早期に評価することが可能であった。また拡散強調MRIの手法を用いるとFDG-PETよりもさらに小さな腫瘍の検出が可能で、ヒトでは5mmの大きさ、動物実験では15mgの腫瘍まで明瞭に描出することができた。拡散強調MRIはPETに比べ多くの病院で簡便に検査でき、放射性被ばくもないことから急速に普及するものと期待される。

Research Products

• [Journal Article] Positron emission tomographic imaging with ^<11>C-choline in differential diagnosis of head and neck tumors : comparison with ^<18>F-FDG PET. (2004)
  • Author(s): Khan, N.
  • Journal Title: Annals of Nuclear Medicine 18 Pages: 409-417
• [Journal Article] Diagnosis of tumor in the nasal cavity and paranasal sinuses with [^<11>C]choline PET : Comparative study with 2-[^<18>F]fluoro-2-deoxy-D-glucose (FDG) PET. (2004)
  • Author(s): Ninomiya, H.
  • Journal Title: Annals of Nuclear Medicine 18 Pages: 29-34
• [Journal Article] The effects of frequency-encoding gradient upon detectablility of the margins and height measurements of normal adult pituitary glands. (2004)
  • Author(s): Taketomi, A.
  • Journal Title: Neuroradiology 46 Pages: 60-64
• [Journal Article] Comparison of ^<11>C-choline PET and FDG PET for the differential diagnosis of malignant tumors. (2004)
  • Author(s): Tian, M.
  • Journal Title: Eur J Nucl Med Mol Imaging 31 Pages: 1064-1072
• [Journal Article] Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study. (2004)
  • Author(s): Tian, M.
  • Journal Title: Eur J Nucl Med Mol Imaging 32 Pages: 5-12
• [Journal Article] The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma. (2004)
  • Author(s): Kato, H.
  • Journal Title: Cancer 103 Pages: 148-156
• [Book] Clinical PET Principles and Applications(Kim, EE.Lee, MC., Inoue, T., Wong, WH.Editors.) (2004)
  • Author(s): Inoue, T.
  • Total Pages: 394
  • Publisher: Springer
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• [Publications] Khan, N: "PET in the follow-up of differentiated thyroid cancer"The British Journal of Radiology. 76. 690-695 (2003)
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• [Publications] Kato H.: "Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma"Cancer. 94. 921-928 (2002)
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• [Publications] H.Zhang: "Oncologic diagnosis of positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET"British Journal of Radiology. (in press). (2002)
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• [Publications] T.Iwasaki: "Immunoscintigraphy of aortic dissection with ^<99m>Tc-labeled murine anti-smooth muscle myosin monoclonal antibody in rats."J Nucl Med. 42. 130-137 (2001)
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