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Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft


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タイトル: Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft
著者: Ukon, Naoyuki 著作を一覧する
Zhao, Songji 著作を一覧する
Yu, Wenwen 著作を一覧する
Shimizu, Yoichi 著作を一覧する
Nishijima, Ken-ichi 著作を一覧する
Kubo, Naoki 著作を一覧する
Kitagawa, Yoshimasa 著作を一覧する
Tamaki, Nagara 著作を一覧する
Higashikawa, Kei 著作を一覧する
Yasui, Hironobu 著作を一覧する
Kuge, Yuji 著作を一覧する
キーワード: Sorafenib
Tumor proliferation
3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT)
Dynamic PET
Renal cell carcinoma xenograft
発行日: 2016年12月12日
出版者: Springer
誌名: EJNMMI research
巻: 6
開始ページ: 90
出版社 DOI: 10.1186/s13550-016-0246-z
抄録: Background: Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-3H(N)]-3'-fluoro-3'-deoxythythymidine ([3H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [18F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [18F]FLT. Results: The dynamic pattern of [18F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [18F]FLT phosphorylation (k3) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [18F]FLT forward transport (K1) to reverse transport (k2), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Conclusions: Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide improved understanding of the biochemical processes involved in tumor responses to therapy.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 久下 裕司


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