2022 Fiscal Year Final Research Report

Novel strategy for treatment of oral cancer based on hypoxia imaging

Research Project

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Project/Area Number	19H03845
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 57060:Surgical dentistry-related
Research Institution	Hokkaido University
Principal Investigator	KITAGAWA Yoshimasa 北海道大学, 歯学研究院, 教授 (00224957)
Co-Investigator(Kenkyū-buntansha)	竹内康人金沢大学, がん進展制御研究所, 助教 (10735187) 大賀則孝北海道大学, 歯学研究院, 助教 (40548202) 佐藤淳北海道大学, 歯学研究院, 准教授 (60319069) 犬伏正幸川崎医科大学, 医学部, 准教授 (70399830) 趙松吉福島県立医科大学, 公私立大学の部局等, 教授 (80374239) 志賀哲北海道大学, アイソトープ総合センター, 客員研究員 (80374495)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	低酸素 / 遺伝子応答 / PET / 口腔がん / 頭頸部がん / FMISO / 分子イメージング
Outline of Final Research Achievements	One of the most important issues to overcome refractory cancer is to identify cancer cells in which the HIF-1/hypoxia-response element (HRE) pathway is activated by reduced oxygen levels. Therefore, the aim of this study is, based on the genetic response to hypoxia, to evaluate two types of hypoxia-targeted PET tracers: [18F]fluoromisonidazole (18F-FMISO) and 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM). The tumor SUV of hypoxia-targeted PET tracers reflected genetic response to hypoxia. The intratumoral distributions of both types of hypoxia-targeted PET tracers showed partial overlap with those of genetic response to hypoxia. We found that HIF-1/HRE activation was mainly observed in the region where both types of hypoxia-targeted PET tracers do not accumulate, suggesting that the importance of focusing on this region.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	腫瘍内環境における低酸素は多くの固形癌の強力な予後因子とされているが、低酸素状態の可視化は極めて困難であった。われわれは低酸素状態で遺伝子応答する癌細胞株を樹立し、動物実験でイメージングに成功した。さらに低酸素分子イメージングとしてFMISO-PETを口腔癌に臨床応用した。FMISO-PETの集積と組織中のHIF-1αの発現が有意に関連していることを世界で初めて明らかにした。術前化学療法の効果の予測、増殖能との関係、低酸素容積と予後との関連も見いだした。