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Article

Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model

  • Authors:
    • Masahiro Murakami
    • Songji Zhao
    • Yan Zhao
    • Wenwen Yu
    • Chowdhury Nusrat Fatema
    • Ken‑Ichi Nishijima
    • Masahiro Yamasaki
    • Mitsuyoshi Takiguchi
    • Nagara Tamaki
    • Yuji Kuge
  • View Affiliations / Copyright

    Affiliations: Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan, Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan, Central Institute of Isotope Science, Hokkaido University, Sapporo, Hokkaido 060‑0815, Japan
  • Pages: 667-672
    |
    Published online on: July 12, 2013
       https://doi.org/10.3892/ol.2013.1459
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Abstract

An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. 18F‑fluorothymidine (18F‑FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase‑1 (TK‑1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki‑67. Mice bearing A498 tumors were assigned to the control and sorafenib‑treated groups and the tumor volume was measured every day. [Methyl‑3H(N)]‑3'‑fluoro‑3'‑deoxythymidine (3H‑FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. 3H‑FLT autoradiography (ARG) and Ki‑67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral 3H‑FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki‑67 IHC. The intratumoral 3H‑FLT uptake levels significantly increased by 2.7‑ and 2.6‑fold on days three and seven following the treatment, while the tumor volume and Ki‑67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK‑1 activity by sorafenib.
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1 

Rini BI: Vascular endothelial growth factor-targeted therapy in renal cell carcinoma: current status and future directions. Clin Cancer Res. 13:1098–1106. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Cáceres W and Cruz-Chacón A: Renal cell carcinoma: molecularly targeted therapy. PR Health Sci J. 30:73–77. 2011.PubMed/NCBI

3 

Chang YS, Adnane J, Trail PA, et al: Sorafenib (BAY 43–9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol. 59:561–574. 2007.

4 

Escudier B, Eisen T, Stadler WM, et al; TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Elias JM: Cell proliferation indexes: a biomarker in solid tumors. Biotech Histochem. 72:78–85. 1997. View Article : Google Scholar : PubMed/NCBI

6 

Gerdes J: Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. Semin Cancer Biol. 1:199–206. 1990.

7 

Scholzen T and Gerdes J: The Ki-67 protein: from the known and the unknown. J Cell Physiol. 182:311–322. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Shields AF, Grierson JR, Dohmen BM, et al: Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 4:1334–1336. 1998.

9 

Toyohara J, Waki A, Takamatsu S, Yonekura Y, Magata Y and Fujibayashi Y: Basis of FLT as a cell proliferation marker: comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines. Nucl Med Biol. 29:281–287. 2002.PubMed/NCBI

10 

Apisarnthanarax S, Alauddin MM, Mourtada F, et al: Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-3H-fluorothymidine using preclinical tumor models. Clin Cancer Res. 12:4590–4597. 2006.PubMed/NCBI

11 

Chao KS: Functional imaging for early prediction of response to chemoradiotherapy: 3′-deoxy-3′-18F-fluorothymidine positron emission tomography - a clinical application model of esophageal cancer. Semin Oncol. 33(6 Suppl 11): S59–S63. 2006.PubMed/NCBI

12 

Chao KS: 3′-deoxy-3′-(18)F-fluorothymidine (FLT) positron emission tomography for early prediction of response to chemoradiotherapy - a clinical application model of esophageal cancer. Semin Oncol. 34(2 Suppl 1): S31–S36. 2007.

13 

Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q and Aboagye EO: Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. Cancer Res. 65:4202–4210. 2005.

14 

Ullrich RT, Zander T, Neumaier B, et al: Early detection of erlotinib treatment response in NSCLC by 3′-deoxy-3′-[F]-fluoro-L-thymidine ([F]FLT) positron emission tomography (PET). PLoS One. 3:e39082008.

15 

Kenny L, Coombes RC, Vigushin DM, Al-Nahhas A, Shousha S and Aboagye EO: Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging. 34:1339–1347. 2007.PubMed/NCBI

16 

Zhao S, Kuge Y, Mochizuki T, et al: Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor. J Nucl Med. 46:675–682. 2005.PubMed/NCBI

17 

Wilhelm SM, Carter C, Tang L, et al: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004.

18 

Buck AK, Herrmann K, Shen C, Dechow T, Schwaiger M and Wester HJ: Molecular imaging of proliferation in vivo: positron emission tomography with [18F]fluorothymidine. Methods. 48:205–215. 2009.

19 

Barwick T, Bencherif B, Mountz JM and Avril N: Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation. Nucl Med Commun. 30:908–917. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Liu G, Jeraj R, Vanderhoek M, et al: Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate. Clin Cancer Res. 17:7634–7644. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Zhang CC, Yan Z, Li W, et al: [(18)F]FLT-PET imaging does not always ‘light up’ proliferating tumor cells. Clin Cancer Res. 18:1303–1312. 2012.

22 

Chalkidou A, Landau DB, Odell EW, Cornelius VR, O’Doherty MJ and Marsden PK: Correlation between Ki-67 immunohistochemistry and 18F-Fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis. Eur J Cancer. 48:3499–3513. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Lee SJ, Kim SY, Chung JH, et al: Induction of thymidine kinase 1 after 5-fluorouracil as a mechanism for 3′-deoxy-3′-[18F]fluorothymidine flare. Biochem Pharmacol. 80:1528–1536. 2010.PubMed/NCBI

24 

Plotnik DA, McLaughlin LJ, Krohn KA and Schwartz JL: The effects of 5-fluoruracil treatment on 3′-fluoro-3′-deoxythymidine (FLT) transport and metabolism in proliferating and non-proliferating cultures of human tumor cells. Nucl Med Biol. 39:970–976. 2012.

25 

Wilson PM, LaBonte MJ, Lenz HJ, Mack PC and Ladner RD: Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer. Mol Cancer Ther. 11:616–628. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Takeuchi A, Shiota M, Tatsugami K, et al: Sorafenib augments cytotoxic effect of S-1 in vitro and in vivo through TS suppression. Cancer Chemother Pharmacol. 68:1557–1564. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Murakami M, Zhao S, Zhao Y, Yu W, Fatema CN, Nishijima KI, Yamasaki M, Takiguchi M, Tamaki N, Kuge Y, Kuge Y, et al: Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model. Oncol Lett 6: 667-672, 2013.
APA
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C.N., Nishijima, K. ... Kuge, Y. (2013). Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model. Oncology Letters, 6, 667-672. https://doi.org/10.3892/ol.2013.1459
MLA
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C. N., Nishijima, K., Yamasaki, M., Takiguchi, M., Tamaki, N., Kuge, Y."Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model". Oncology Letters 6.3 (2013): 667-672.
Chicago
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C. N., Nishijima, K., Yamasaki, M., Takiguchi, M., Tamaki, N., Kuge, Y."Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model". Oncology Letters 6, no. 3 (2013): 667-672. https://doi.org/10.3892/ol.2013.1459
Copy and paste a formatted citation
x
Spandidos Publications style
Murakami M, Zhao S, Zhao Y, Yu W, Fatema CN, Nishijima KI, Yamasaki M, Takiguchi M, Tamaki N, Kuge Y, Kuge Y, et al: Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model. Oncol Lett 6: 667-672, 2013.
APA
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C.N., Nishijima, K. ... Kuge, Y. (2013). Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model. Oncology Letters, 6, 667-672. https://doi.org/10.3892/ol.2013.1459
MLA
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C. N., Nishijima, K., Yamasaki, M., Takiguchi, M., Tamaki, N., Kuge, Y."Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model". Oncology Letters 6.3 (2013): 667-672.
Chicago
Murakami, M., Zhao, S., Zhao, Y., Yu, W., Fatema, C. N., Nishijima, K., Yamasaki, M., Takiguchi, M., Tamaki, N., Kuge, Y."Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model". Oncology Letters 6, no. 3 (2013): 667-672. https://doi.org/10.3892/ol.2013.1459
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