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Article

Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts

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

    Affiliations: Department of Oral Diagnosis and Medicine, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8586, 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, Department of Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8638, Japan, Department of Integrated Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8638, Japan
  • Pages: 2341-2346
    |
    Published online on: June 12, 2017
       https://doi.org/10.3892/ol.2017.6371
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Abstract

A mechanistic dissociation exists between tumor starvation and vascular normalization after antiangiogenic therapy. Thus, improved understanding of tumor responses (tumor starvation or vascular normalization) is important for optimizing treatment strategies. 18F‑fluoromisonidazole (18F‑FMISO) is widely used for imaging tumor hypoxia. To clarify the tumor response to the antiangiogenic drug sorafenib, the present study evaluated the changes in the tumor oxygen state using 18F‑FMISO in mice bearing a renal cell carcinoma xenograft (A498). Mice bearing A498 xenografts were assigned to the control and three sorafenib‑treatment groups and administered sorafenib (0, 10, 20 or 40 mg/kg/day, per os) once daily for 3 days. Following one day after the final administration, the mice were injected with 18F‑FMISO and pimonidazole (a hypoxia marker). 18F‑FMISO accumulation in the tumor was determined by autoradiography. Immunohistochemistry of pimonidazole and cluster of differentiation (CD)31 (a vascular marker) was also performed. 18F-FMISO accumulation levels in the tumor significantly increased by 4.3‑, 8.4‑ and 8.6‑fold compared with in the control group following 10, 20 and 40 mg/kg sorafenib treatments, respectively [0.07±0.04, 0.32±0.11, 0.62±0.15 and 0.63±0.23 (%ID/m2) x kg for the control, and 10, 20 and 40 mg treatments, respectively; all P<0.0083 vs. the control]. The number of pimonidazole‑positive cells also significantly increased by 6.8‑, 12.3‑ and 20.2‑fold compared with in the control group following 10, 20 and 40 mg/kg sorafenib treatments, respectively (0.78±0.79, 5.36±2.29, 9.66±1.58 and 15.85±4.59% pimonidazole‑positive cells; all P<0.0083 vs. the control). The number of microvessels in tumors markedly decreased to 33.5, 17.6, and 14.0% of the control following 10, 20 and 40 mg/kg sorafenib treatments, respectively (17.1±2.5, 5.7±1.0, 3.0±1.0 and 2.4±0.3 vessels/mm2; P<0.0083 vs. the control). The 18F‑FMISO expression level in the tumor increased sorafenib‑dose‑dependently, which is consistent with the increase in the number of pimonidazole‑positive cells and decrease in the number of microvessels. These findings indicated that the present sorafenib treatment protocol induces ‘tumor hypoxia/starvation’ in the renal cell carcinoma xenograft (A498) due to its antiangiogenic properties.
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View References

1 

Carmeliet P and Jain RK: Angiogenesis in cancer and other diseases. Nature. 407:249–257. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science. 307:58–62. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Ma J and Waxman DJ: Combination of antiangiogenesis with chemotherapy for more effective cancer treatment. Mol Cancer Ther. 7:3670–3684. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Takimoto CH and Awada A: Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: A review of clinical trials. Cancer Chemother Pharmacol. 61:535–548. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Folkman J: Tumor angiogenesis: Therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI

6 

Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D and Jain RK: Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 91:1071–1121. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Offermanns S and Rosenthal W: Encyclopedia of Molecular Pharmacology. 2nd. Berlin: Springer-Verlag; 2008, View Article : Google Scholar

8 

Oehler C, O'Donoghue JA, Russell J, Zanzonico P, Lorenzen S, Ling CC and Carlin S: 18F-fluomisonidazole PET imaging as a biomarker for the response to 5,6-dimethylx-anthenone-4-acetic acid in colorectal xenograft tumors. J Nucl Med. 52:437–444. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Lawrentschuk N, Poon AM, Foo SS, Putra LG, Murone C, Davis ID, Bolton DM and Scott AM: Assessing regional hypoxia in human renal tumors using 18F-fluoromisonidazole positron emission tomography. BJU Int. 96:540–546. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, Machulla HJ and Bares R: Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small lung cancer and head and neck cancer before radiotherapy. J Nucl Med. 46:253–260. 2005.PubMed/NCBI

11 

Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N and Kuge Y: Evaluation of changes in the tumor microenvironment after sorafenib therapy by sequential histology and 18F-fluoromisonidazole hypoxia imaging in renal cell carcinoma. Int J Oncol. 41:1593–1600. 2012.PubMed/NCBI

12 

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Tang G, Wang M, Tang X, Gan M and Luo L: Fully automated one-pot synthesis of [18F] fluoromisonidazole. Nucl Med Biol. 32:553–558. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Oh SJ, Chi DY, Mosdzianowski C, Kim JY, Gil HS, Kang SH, Ryu JS and Moon DH: Fully automated synthesis of [18F] fluoromisonidazole using a conventional [18F] FDG module. Nucl Med Biol. 32:899–905. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Zhao S, Kuge Y, Mochizuki T, Takahashi T, Nakada K, Sato M, Takei T and Tamaki N: 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

16 

Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP and Wahl RL: Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma. I. Are inflammatory cells important? J Nucl Med. 36:1854–1861. 1995.PubMed/NCBI

17 

Toyama H, Ichise M, Liow JS, Modell KJ, Vines DC, Esaki T, Cook M, Seidel J, Sokoloff L, Green MV and Innis RB: Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography. J Nucl Med. 45:1398–1405. 2004.PubMed/NCBI

18 

Shinojima T, Oya M, Takayanagi A, Mizuno R, Shimizu N and Murai M: Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha. Carcinogenesis. 28:529–536. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Iliopoulos O, Kibel A, Gray S and Kaelin WG Jr: Tumour suppression by the human von Hippel-Lindau gene product. Nat Med. 1:822–826. 1995. View Article : Google Scholar : PubMed/NCBI

20 

Kaelin WG Jr: Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer. 2:673–682. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, 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. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu W, Zhao S, Zhao Y, Fatema CN, Murakami M, Nishijima KI, Kitagawa Y, Tamaki N and Kuge Y: Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts. Oncol Lett 14: 2341-2346, 2017.
APA
Yu, W., Zhao, S., Zhao, Y., Fatema, C.N., Murakami, M., Nishijima, K. ... Kuge, Y. (2017). Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts. Oncology Letters, 14, 2341-2346. https://doi.org/10.3892/ol.2017.6371
MLA
Yu, W., Zhao, S., Zhao, Y., Fatema, C. N., Murakami, M., Nishijima, K., Kitagawa, Y., Tamaki, N., Kuge, Y."Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts". Oncology Letters 14.2 (2017): 2341-2346.
Chicago
Yu, W., Zhao, S., Zhao, Y., Fatema, C. N., Murakami, M., Nishijima, K., Kitagawa, Y., Tamaki, N., Kuge, Y."Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts". Oncology Letters 14, no. 2 (2017): 2341-2346. https://doi.org/10.3892/ol.2017.6371
Copy and paste a formatted citation
x
Spandidos Publications style
Yu W, Zhao S, Zhao Y, Fatema CN, Murakami M, Nishijima KI, Kitagawa Y, Tamaki N and Kuge Y: Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts. Oncol Lett 14: 2341-2346, 2017.
APA
Yu, W., Zhao, S., Zhao, Y., Fatema, C.N., Murakami, M., Nishijima, K. ... Kuge, Y. (2017). Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts. Oncology Letters, 14, 2341-2346. https://doi.org/10.3892/ol.2017.6371
MLA
Yu, W., Zhao, S., Zhao, Y., Fatema, C. N., Murakami, M., Nishijima, K., Kitagawa, Y., Tamaki, N., Kuge, Y."Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts". Oncology Letters 14.2 (2017): 2341-2346.
Chicago
Yu, W., Zhao, S., Zhao, Y., Fatema, C. N., Murakami, M., Nishijima, K., Kitagawa, Y., Tamaki, N., Kuge, Y."Changes in tumor oxygen state after sorafenib therapy evaluated by 18F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts". Oncology Letters 14, no. 2 (2017): 2341-2346. https://doi.org/10.3892/ol.2017.6371
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