Development of alpha-particle therapy for pancreas cancer with stem cell-targeting 211At-labeled antibody
Project/Area Number |
16H05393
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Radiation science
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Research Institution | Fukushima Medical University |
Principal Investigator |
Oriuchi Noboru 福島県立医科大学, 公私立大学の部局等, 教授 (40292586)
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Co-Investigator(Kenkyū-buntansha) |
久保 均 福島県立医科大学, 公私立大学の部局等, 教授 (00325292)
高橋 和弘 慶應義塾大学, 医学部(信濃町), 特任准教授 (20370257)
趙 松吉 福島県立医科大学, 公私立大学の部局等, 教授 (80374239)
大島 康宏 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 放射線生物応用研究部, 主任研究員(定常) (00588676)
石岡 典子 国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 放射線生物応用研究部, 上席研究員(定常) (30354963)
富永 英之 福島県立医科大学, 公私立大学の部局等, 准教授 (00393348)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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Keywords | 核医学治療 / α線 / RI内用療法 / アスタチン / 211At / 膵癌 / 放射免疫療法 / 癌幹細胞 / At-211 / アスタチン211 / CXCR4 / CXCX4 / 標的アイソトープ治療 / がん幹細胞 / 標的RI治療 / Lu-177 |
Outline of Final Research Achievements |
The study evaluated biokinetics of 211At-labeled anti-CXCR4 antibody (211At-CXCR4) in the tumor xenograft to see the possibility of cancer stem cell targeted radioimmunotherapy. Human pancreas cancer cell lines and acute leukemia cell line were maintained for in vivo examination. Anti-CXCR4 monoclinal antibody was labeled with 125I and 211At. Suspension of tumor cells were injected subcutaneously in the athymic Balb/c mice. The animal study was approved by the Animal Care Committee and were performed in accordance with institutional guidelines. At the designated time after injection of 125I, or 211At-CXCR4 into the tumor-bearing mice, aliquots of blood and organs of interest were excised to calculate %ID/g. 211At-labeled anti-CXCR4 antibody was stably radiolabeled and biodistribution of 211At-CXCR4 as well as tumor uptake was similar to that of 125I-CXCR4, suggesting possibility of radioimmunotherapy targeting cancer stem cells.
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Academic Significance and Societal Importance of the Research Achievements |
核医学治療に用いるRIのなかで、α線は優れたエネルギー特性によって効果的にDNA二重鎖を切断する一方、組織内飛程が短いため正常細胞の障害が少ないことから、従来のβ線による治療で制御できない固形癌に対する新たな治療として有望である。 本研究はα線核種標識抗体による難治性腫瘍の治療開発を目標とする。がん幹細胞を認識する211At標識抗体の腫瘍モデルにおける体内動態ならびに腫瘍集積は125I標識抗体と相同であることが確認されたことから、がん幹細胞に対する211At標識抗体による治療の有効性が示唆された。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] A randomised phase II trial of capecitabine plus cisplatin versus S-1 plus cisplatin as a first-line treatment for advanced gastric cancer: Capecitabine plus cisplatin ascertainment versus S-1 plus cisplatin randomised PII trial (XParTS II).2018
Author(s)
Nishikawa K, Tsuburaya A, Yoshikawa T, Kobayashi M, Kawada J, Fukushima R, Matsui T, Tanabe K, Yamaguchi K, Yoshino S, et al
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Journal Title
Eur J Cancer
Volume: 101
Pages: 220-228
DOI
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Peer Reviewed
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[Journal Article] Optimized workflow and imaging protocols for whole-body oncologic PET/MRI.2016
Author(s)
Ishii S, Hara T, Nanbu T, Suenaga H, Sugawara S, Kuroiwa D, Sekino H, Miyajima M, Kubo H, Oriuchi N, Ito H
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Journal Title
Jpn J Radiol
Volume: 34
Issue: 11
Pages: 754-762
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma.2016
Author(s)
Ohshima Y, Kaira K, Yamaguchi A, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yokobori T, Miyazaki T, Asao T, Tsushima Y, Kuwano H, Ishioka NS.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 10
Pages: 1499-1505
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography.2016
Author(s)
Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Kato Y, Oriuchi N, Nagamori S, Kanai Y.
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Journal Title
J Pharmacol Sci.
Volume: 130
Issue: 2
Pages: 101-109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Biodistribution of free 211At and meta-[211At]astatobenzylguanidine (MABG) in normal mice2018
Author(s)
Songji Zhao, Miho Aoki, Kohshin Washiyama, Naoyuki Ukon, Chengbao Tan, Saki Shimoyama, Hitoshi Kubo, Noboru Oriuchi, Kazuhiro Takahashi, Hiroshi Ito, Seiichi Takenoshita
Organizer
第58回日本核医学会総会
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