Prediction of response to anticancer therapy by thymidine phosphorylase imaging: pre-clinical proof of concept
| Project/Area Number |
16K10335
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
Zhao Songji 福島県立医科大学, 公私立大学の部局等, 教授 (80374239)
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| Co-Investigator(Kenkyū-buntansha) |
久下 裕司 北海道大学, アイソトープ総合センター, 教授 (70321958)
東川 桂 北海道大学, アイソトープ総合センター, 助教 (10756878)
志水 陽一 京都大学, 医学研究科, 助教 (90634212)
志賀 哲 北海道大学, 医学研究院, 准教授 (80374495)
北川 善政 北海道大学, 歯学研究院, 教授 (00224957)
大倉 一枝 北海道医療大学, 薬学部, 教授 (60094827)
秋澤 宏行 昭和薬科大学, 薬学部, 教授 (90311795)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | チミジンホスホリラーゼ（TP） / ヨウ素標識IIMU / 核医学診断薬 / SPECTイメージング / 5－フルオロウラシル（5-FU) / プロドラッグ / 抗がん剤Paclitaxel / 担癌モデル動物 / 5-フルオロウラシル（5-FU） / ５－FUプロドラッグ / がんの核医学的分子イメージング / IIMU / ＰＥＴ／ＳＰＥＣＴ / 5-フルオロウラシル |
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| Outline of Final Research Achievements |
Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway, and its expression is upregulated in a wide variety of solid tumors. TP expression correlates well with tumor malignancy and is essential for the bioactivation of 5-fluorouracil and its prodrugs including capecitabine in tumors. Capecitabine-based chemotherapies have been reported to be effective in tumors expressing high TP levels. Radio- and chemotherapies including paclitaxel may induce the expression of TP in tumors. We have developed a radio-iodinated uracil derivative with TP inhibitory potency (125/123I-IIMU). In this study, we evaluated whether TP imaging could predict the response to an anticancer therapy by estimating TP expression levels in tumor tissues. In vivo studies showed that paclitaxel increased TP expression levels and 125I-IIMU uptake in tumor tissues. Therefore, TP imaging could be used for predicting the response to an anticancer therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
我々が開発した123I-IIMUを用いたTP画像化法は、核医学の特徴である非侵襲性、かつ腫瘍組織のTP発現量を感度よく定量的に評価できるため、世界で初めての5-FUやそのプロドラッグの治療効果を予測可能にすることが本研究の学術的意義がある。本研究において、IIMUを用いたTP画像化によって、5-FUやそのプロドラッグによる治療効果予測が可能なことが示されれば、速やかに臨床応用を開始できるため、効果のない無駄な治療を避け、速やかに他の治療方針を決定することで、患者ごとに最適な個別化医療が実現できるとともに、医療経済効果、医療の質の向上にも貢献ができるし、医療戦略の革新となることが期待される。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models2019
Author(s)
Zhao S, Yu W, Ukon N, Tan C, Nishijima K, Shimizu Y, Higashikawa K, Shiga T, Yamashita H, Tamaki N, Kuge Y.
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Journal Title
EJNMMI Res
Volume: in press
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] [18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia2018
Author(s)
Tan C, Zhao S, Higashikawa K, Wang Z, Kawabori M, Abumiya T, Nakayama N, Kazumata K, Ukon N, Yasui H, Tamaki N, Kuge Y, Shichinohe H, Houkin K
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Journal Title
EJNMMI Res
Volume: ８
Issue: 1
Pages: 35-35
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Biodistribution of free 211At and meta-[211At]astatobenzylguanidine (MABG) in normal mice.2018
Author(s)
Zhao S, Aoki M, Washiyaoyma K, Ukon N, Tan C, Shimama S, Kubo H, Oriuchi N, Takahashi K, Ito H, Takenoshita S.
Organizer
第58回日本核医学会学術総会
Related Report
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