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Evaluation of Antiangiogenic Effects of a New Synthetic Candidate Drug KR-31831 on Xenografted Ovarian Carcinoma Using Dynamic Contrast Enhanced MRI

  • Yang, Je-Hoon (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jae-Hun (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Im, Geun-Ho (Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center) ;
  • Heo, Hye-Jung (Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center) ;
  • Yoon, Se-Ra (Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center) ;
  • Lee, Jae-Won (Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center) ;
  • Lee, Jung-Hee (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeon, Pyoung (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 발행 : 2011.10.01

초록

Objective: The purpose of this research was to investigate the anti-angiogenic inhibitory effect of KR-31831, a newly developed anti-angiogenic agent, on an in vivo human ovarian carcinoma model using dynamic contrast-enhanced (DCE) MRI. Materials and Methods: Xenografted ovarian tumors were established by subcutaneous injection of SKOV3 cells into mice. The mice were treated daily with KR-31831 at 50 mg/kg for 21 days. Tumor tissues were excised corresponding to the DCE-MRI sections for evaluation of MVD with CD31 immunohistochemistry. All in vivo MRIs were performed on a 7.0 Tesla micro-MRI System. DCE-MRI was acquired prior to initiating treatment with KR-31831 and again on days 3 and 21 after treatment. The permeability parameters ($K^{trans},\;V_2$, and $V_p$) were estimated using a pharmacokinetic model. Results: Qualitatively, the $K^{trans}$ parametric mapping showed different changes before and after treatment with KR-31831 in the treatment group. For quantification of this change, the median of $K^{trans}$ values were compared before and after treatments in the control and KR-31831-treated groups. A non-parametric statistical test (Wilcoxon signed-rank test) showed decreasing $K^{trans}$ values on day 21 compared to days 0 and 3 in the KR-31831-treated group (p < 0.05), whereas there was no significant difference in the control group (p = 0.84). Conclusion: Our results suggest that DCE-MRI can be a useful tool by which to evaluate the anti-angiogenic effect of KR-31831 on a xenografted human ovarian carcinoma model.

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참고문헌

  1. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990;82:4-6 https://doi.org/10.1093/jnci/82.1.4
  2. Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997;390:404-407 https://doi.org/10.1038/37126
  3. Ko EY, Lee SH, Kim HH, Kim SM, Shin MJ, Kim N, et al. Evaluation of tumor angiogenesis with a second-generation US contrast medium in a rat breast tumor model. Korean J Radiol 2008;9:243-249 https://doi.org/10.3348/kjr.2008.9.3.243
  4. Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, et al. Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to plateletderived growth factor. Proc Natl Acad Sci U S A 1990;87:2628-2632 https://doi.org/10.1073/pnas.87.7.2628
  5. Fox SB, Gasparini G, Harris AL. Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol 2001;2:278-289 https://doi.org/10.1016/S1470-2045(00)00323-5
  6. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997;18:4-25 https://doi.org/10.1210/er.18.1.4
  7. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851-858 https://doi.org/10.1016/0006-291X(89)92678-8
  8. Plouet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 1989;8:3801-3806
  9. Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei J, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000;60:2178-2189
  10. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146:1029-1039
  11. Prewett M, Huber J, Li Y, Santiago A, O'Connor W, King K, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999;59:5209-5218
  12. Kozin SV, Boucher Y, Hicklin DJ, Bohlen P, Jain RK, Suit HD. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res 2001;61:39-44
  13. Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am J Pathol 1998;153:1249-1256 https://doi.org/10.1016/S0002-9440(10)65669-6
  14. Park SY, Seo EH, Song HS, Jung SY, Lee YK, Yi KY, et al. KR-31831, benzopyran derivative, inhibits VEGF-induced angiogenesis of HUVECs through suppressing KDR expression. Int J Oncol 2008;32:1311-1315
  15. Yi EY, Park SY, Song HS, Son MJ, Yi KY, Yoo SE, et al. KR- 31831, a new synthetic anti-ischemic agent, inhibits in vivo and in vitro angiogenesis. Exp Mol Med 2006;38:502-508 https://doi.org/10.1038/emm.2006.59
  16. Kim HH, Paek IB, Ji HY, Lee S, Yi KY, Lee HS. Metabolism of a novel antiangiogenic agent KR-31831 in rats using liquid chromatography-electrospray mass spectrometry. J Sep Sci 2005;28:1818-1822 https://doi.org/10.1002/jssc.200500159
  17. Kim SJ, Lee HI, Ji HY, Moon Y, Paek IB, Lee S, et al. Pharmacokinetics of a novel antiangiogenic agent KR-31831 in rats. Biopharm Drug Dispos 2005;26:21-26 https://doi.org/10.1002/bdd.427
  18. O'Connor JP, Jackson A, Parker GJ, Jayson GC. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Br J Cancer 2007;96:189-195 https://doi.org/10.1038/sj.bjc.6603515
  19. Zahra MA, Hollingsworth KG, Sala E, Lomas DJ, Tan LT. Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy. Lancet Oncol 2007;8:63-74 https://doi.org/10.1016/S1470-2045(06)71012-9
  20. Pedersen M, Morkenborg J, Jensen FT, Stodkilde-Jorgensen H, Djurhuus JC, Frokiaer J. In vivo measurements of relaxivities in the rat kidney cortex. J Magn Reson Imaging 2000;12:289-296 https://doi.org/10.1002/1522-2586(200008)12:2<289::AID-JMRI11>3.0.CO;2-O
  21. Deoni SC, Rutt BK, Peters TM. Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state. Magn Reson Med 2003;49:515-526 https://doi.org/10.1002/mrm.10407
  22. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 1999;10:223-232 https://doi.org/10.1002/(SICI)1522-2586(199909)10:3<223::AID-JMRI2>3.0.CO;2-S
  23. Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 1996;29:162-173 https://doi.org/10.1006/cbmr.1996.0014
  24. Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, et al. Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res 2009;15:5426-5434 https://doi.org/10.1158/1078-0432.CCR-09-0287
  25. Pandya NM, Dhalla NS, Santani DD. Angiogenesis--a new target for future therapy. Vascul Pharmacol 2006;44:265-274 https://doi.org/10.1016/j.vph.2006.01.005
  26. Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-4599
  27. Strawn LM, McMahon G, App H, Schreck R, Kuchler WR, Longhi MP, et al. Flk-1 as a target for tumor growth inhibition. Cancer Res 1996;56:3540-3545
  28. Jun HY, Yin HH, Kim SH, Park SH, Kim HS, Yoon KH. Visualization of tumor angiogenesis using MR imaging contrast agent Gd-DTPA-anti-VEGF receptor 2 antibody conjugate in a mouse tumor model. Korean J Radiol 2010;11:449-456 https://doi.org/10.3348/kjr.2010.11.4.449
  29. Xiong HQ, Herbst R, Faria SC, Scholz C, Davis D, Jackson EF, et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs 2004;22:459-466
  30. Thomassin-Naggara I, Bazot M, Darai E, Callard P, Thomassin J, Cuenod CA. Epithelial ovarian tumors: value of dynamic contrast-enhanced MR imaging and correlation with tumor angiogenesis. Radiology 2008;248:148-159 https://doi.org/10.1148/radiol.2481071120
  31. Hillman GG, Singh-Gupta V, Zhang H, Al-Bashir AK, Katkuri Y, Li M, et al. Dynamic contrast-enhanced magnetic resonance imaging of vascular changes induced by sunitinib in papillary renal cell carcinoma xenograft tumors. Neoplasia 2009;11:910-920
  32. Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 1991;17:357-367 https://doi.org/10.1002/mrm.1910170208
  33. Brix G, Semmler W, Port R, Schad LR, Layer G, Lorenz WJ. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr 1991;15:621-628 https://doi.org/10.1097/00004728-199107000-00018
  34. Larsson HB, Stubgaard M, Frederiksen JL, Jensen M, Henriksen O, Paulson OB. Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med 1990;16:117-131 https://doi.org/10.1002/mrm.1910160111

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