2018 Fiscal Year Final Research Report

Development and application of novel chemical compounds to materialize the cancer theranostics

Research Project

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Project/Area Number	17K19670
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Research Field	General internal medicine and related fields
Research Institution	Kyoto Pharmaceutical University
Principal Investigator	Yasui Hiroyuki 京都薬科大学, 薬学部, 教授 (20278443)
Co-Investigator(Kenkyū-buntansha)	木村寛之京都薬科大学, 薬学部, 准教授 (50437240) 有光健治京都薬科大学, 薬学部, 助教 (50707693) 戸崎充男京都大学, 環境安全保健機構, 准教授 (70207570) 河嶋秀和京都薬科大学, 薬学部, 准教授 (70359438) 中田晋京都薬科大学, 薬学部, 准教授 (80590695)
Project Period (FY)	2017-06-30 – 2019-03-31
Keywords	がんTheranostics / フレキシブルTheranosticsプローブ / EGFR / EphA2 / PET/SPECTイメージング / EGFRvIII / Fzd3
Outline of Final Research Achievements	We have succeeded to design and synthesize several kinds of low molecular-weight organic RI-unlabeled compounds as potential candidates of imaging probes and therapeutic ligands targeted for the receptors such as EGFR,FGFR, and EphA2 as one of the tyrosine kinase type-receptor. Especially, the research and development of compound A as an imaging probe targeted for EGFR were most proceeded among this project, where the PET/CT imaging with F-18-labeled compound A indicated the faster hepatic metabolism and gradual distribution in the bones of brain skull and whole-body. If we use compound A for diagnosis of lung cancer, its distribution and accumulation in normal lung tissues will lead to the false positive diagnosis by the higher background levels and unclear contrasts. Then, we decided that the optimum time points for PET/CT imaging of lung cancer would be 120 min after i.v. injection of compound A. In conclusion, we have planned to carry out a patent application of compound A.
Free Research Field	薬学
Academic Significance and Societal Importance of the Research Achievements	がん治療を目的とした新規化合物の開発については、腫瘍細胞に対する増殖抑制効果や細胞死誘導効果をインビトロ実験系により解析を進める必要や、薬理効果をインビボ実験系で評価する検討も必要ではあるが、最優先課題であった、がんTheranosticプローブとして有望なリード化合物を以下の様に創製することに成功した。１）EGFRを標的とした低分子化合物A（肺がんのPET撮像に有効）、２）EGFRを標的としたTheranosticプローブであるモノクローナル抗体-キレート化合物（In-111, Y-90によるRI標識が可能）、３）EphA2を標的とした新規の低分子化合物B（乳がんのPET撮像に有効）。