RT Journal Article
SR Electronic
T1 Evaluation of <sup>64</sup>Cu-ATSM for an internal radiotherapy agent: <sup>64</sup>Cu-ATSM treatment reduces CD133<sup>+</sup> highly tumorigenic cells and metastatic ability of tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 175
OP 175
VO 51
IS supplement 2
A1 Yoshii, Yukie
A1 Furukawa, Takako
A1 Kiyono, Yasushi
A1 Watanabe, Ryo
A1 Mori, Tetsuya
A1 Yoshii, Hiroshi
A1 Okazawa, Hidehiko
A1 Welch, Michael
A1 Fujibayashi, Yasuhisa
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/175.abstract
AB 175 Objectives 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a potential PET imaging agent of hypoxic tumor and also reported to be a possible agent for internal radiotherapy. We have shown that 64Cu-ATSM preferentially localizes in low vascular-regions with a high density of CD133+ cells possessing characteristics of cancer stem cells (CSCs), in a mouse colon carcinoma (Colon-26) model. In this study, we evaluated therapeutic effect of 64Cu-ATSM in CD133+ cells using this model. Methods Internal radiotherapy with 64Cu-ATSM was performed using mice bearing a 1-week-old Colon-26 tumor. Systemic administration of 37 MBq or 0 MBq of 64Cu-ATSM was conducted twice with a 1-week interval (day 0-7). At day 19, the size of remained tumors was measured, and flow cytometry analysis and experimental lung metastatic assay was performed. Therapeutic effect of 64Cu-ATSM on sorted CD133+ and CD133- cells was also examined. Results Volume of 64Cu-ATSM-treated tumors became 14-fold lower than that of untreated tumors. Percentage of CD133+ cells in 64Cu-ATSM-treated tumors was decreased, compared with that in untreated tumors. Cells from 64Cu-ATSM-treated tumors showed lower metastatic ability in lung of mouse, compared to untreated tumors. 64Cu-ATSM accumulated in CD133+ and CD133- cells under hypoxia and the incorporation of 64Cu-ATSM under hypoxia caused a decrease of survival fraction in both CD133+ and CD133- cells. Conclusions 64Cu-ATSM administration reduced not only tumor volume but also proportion of CD133+ cells and metastatic ability of tumors. 64Cu-ATSM treatment was effective to both CD133+ and CD133- cells under hypoxia. Therefore, 64Cu-ATSM would be a promising agent for internal radiotherapy affecting regions with a high density of CD133+ cells, assumed to be CSCs