がん幹細胞(CSC)は唯一重粒子で殺傷可能と思われるが重粒子線治療では
がん幹細胞の位置がわからないとどうにもならない。
それができるようになった。福井大学での研究開発だ。
以前から64CuASTMという薬剤は低酸素主要のイメージングに使われていたが
低酸素腫瘍とがん幹細胞が深い関係にあるのではないかと考えるのは自然で
そのPET画像とがん幹細胞マーカーであるCD133の関係を調べてみたらピタリと
あたったわけである

これで腫瘍のなかのがん幹細胞(CSC)に重みをつけて照射すれば
転移や再発をより確実に防げるはずである。
そのような治療法はX線治療や陽子線治療と大きな差別化をはかることが可能である。

資料 福井大学の論文:
http://jnumedmtg.snmjournals.org/cgi/content/short/50/2_MeetingAbstracts/1554

Hypoxia imaging agent 64Cu-ATSM visualizes cancer stem cell-rich regions within tumors

Yukie Yoshii1, Yasushi Kiyono1, Atsuo Waki1, Tetsuya Mori1, Hiroshi Yoshii1, Takako Furukawa2, Myungmi Oh1, Masato Kobayashi1, Michael J. Welch3 and Yasuhisa Fujibayashi1

1 University of Fukui, BIRC, Fukui, Japan 2 National Institute of Radiological Sciences, MIC, Chiba, Japan 3 Washington University, MIR, St. Louis, MO

1554

Objectives: 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a PET imaging agent targeting tumor hypoxia. It is known that tumor hypoxia assessed by Cu-ATSM is associated with tumor malignant behavior, such as resistance to therapy and metastasis ability. Recent studies demonstrated that the tumor characteristics of therapeutic resistance and metastasis ability would be attributed to so-called cancer stem cells. Based on these understandings, we hypothesized that tumor hypoxic regions visualized by 64Cu-ATSM would contain higher proportions of cancer stem cells than other tumor regions. In this study, we examined distribution of cancer stem cells within tumors and compared it with accumulations of 64Cu-ATSM and 18FDG.

Methods: Double-tracer autoradiography and immunohistchemistry was performed with mouse colon carcinoma (Colon-26) tumor-bearing mice. In autoradiography, mixture of 74 MBq of 18FDG and 0.37 MBq of 64Cu-ATSM was i.v. injected. CD133 was used as a cancer stem cell marker, which reflected typical characteristics of cancer stem cells in Colon-26 cells.

Results: Percentage of CD133+ cells was high in order of 64Cu-ATSM high uptake regions >64Cu-ATSM middle uptake regions > 64Cu-ATSM low uptake regions > 18FDG high uptake regions within Colon-26 tumors. The density of CD133+ cells was 11-fold higher in 64Cu-ATSM high uptake regions than in 18FDG high uptake regions.

Conclusions: 64Cu-ATSM accumulating hypoxic regions matched CD133+ cell-rich regions within Colon-26 tumors. Our findings suggested that 64Cu-ATSM is a potential imaging agent for cancer stem cell-rich regions within tumors.

Research Support: R.W. helps 64Cu-ATSM synthesis.