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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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Title: Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft
Authors: Ukon, Naoyuki Browse this author
Zhao, Songji Browse this author →KAKEN DB
Yu, Wenwen Browse this author
Shimizu, Yoichi Browse this author →KAKEN DB
Nishijima, Ken-ichi Browse this author
Kubo, Naoki Browse this author →KAKEN DB
Kitagawa, Yoshimasa Browse this author →KAKEN DB
Tamaki, Nagara Browse this author →KAKEN DB
Higashikawa, Kei Browse this author
Yasui, Hironobu Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: Sorafenib
Tumor proliferation
3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT)
Dynamic PET
Renal cell carcinoma xenograft
Issue Date: 12-Dec-2016
Publisher: Springer
Journal Title: EJNMMI research
Volume: 6
Start Page: 90
Publisher DOI: 10.1186/s13550-016-0246-z
Abstract: 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.
Type: article
Appears in Collections:アイソトープ総合センター (Central Institute of Isotope Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 久下 裕司

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