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

Ukon, Naoyuki; Zhao, Songji; Yu, Wenwen et al.

EJNMMI research, 2016, 6, 90

Permalink : https://hdl.handle.net/2115/64568

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アクセス権
open access
URI
https://hdl.handle.net/2115/64568
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 ; Zhao, Songji ; Yu, Wenwen ; Shimizu, Yoichi ; Nishijima, Ken-ichi ; Kubo, Naoki ; Kitagawa, Yoshimasa ; Tamaki, Nagara ; Higashikawa, Kei ; Yasui, Hironobu ; Kuge, Yuji
著者名
Ukon, Naoyuki
e-Rad_Researcher
80374239
著者名
Zhao, Songji
著者名
Yu, Wenwen
e-Rad_Researcher
90634212
著者名
Shimizu, Yoichi
著者名
Nishijima, Ken-ichi
e-Rad_Researcher
80241389
著者名
Kubo, Naoki
e-Rad_Researcher
00224957
著者名
Kitagawa, Yoshimasa
e-Rad_Researcher
30171888
著者名
Tamaki, Nagara
著者名
Higashikawa, Kei
e-Rad_Researcher
10570228
著者名
Yasui, Hironobu
e-Rad_Researcher
70321958
著者名
Kuge, Yuji
言語
英語
キーワード
Sorafenib
Tumor proliferation
3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT)
Dynamic PET
Renal cell carcinoma xenograft
発行日
2016-12-12
出版者
Springer
収録物名
EJNMMI research
巻(号)
6
ページ
90
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.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution 4.0 International
PISSN
2191-219X
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1186/s13550-016-0246-z