Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3939
標題: In vivo fluorescent imaging of breast cancer xenografts in a murine model: comparison with high-resolution sonography
小鼠移植模型中乳癌的活體螢光影像:與高解析超音波之比較
作者: 顏宗賢
Yen, Tsung-Hsien
關鍵字: In vivo fluorescent imaging;活體螢光影像;breast cancer;high-resolution sonography;乳癌;高解析超音波
出版社: 生醫工程研究所
引用: 1. 行政院衛生署國民健康局中華民國癌症登記報告(92-95年)。 2. T. Fischer, I. Gemeinhardt, S. Wagner, D. V. Stieglitz, J. Schnorr, K.-G. A. Hermann, B. Ebert, D. Petzelt, R. MacDonald, K. Licha, M. schirner, V. Krenn, T. Kamradt, M. Taupitz, Assessment of unspecific near-infrared dyes in laser induced fluorescence imaging of experimental arthritis. Academic Radiology, 13, 4-13, 2006. 3. 國民健康局http://www.bhp.doh.gov.tw/BHPnet/Portal/ 4. 楊宛霖、林幸慧:乳癌高危險群之評估及處置。基層醫療, 21(3),68-71, 2006。 5. 乳癌防治基金會 http://www.breastcf.org.tw/ 6. CARESENG.COM http://www.careseng.com/cn/indexc.html 7. Berg, W. A., Gutierrez, L., NessAiver, M. S., et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology, 233(3),830–849, 2004. 8. Kriege, M., Brekelmans, C. T. M., Boetes, C., et al. Efficacy of MRI and mammography for breast cancer screening in women with a familial or genetic predisposition. N. Engl. J. Med., 351, 427–437, 2004. 9. G. J. R. Porter, A. J. Evans, E. J. Cornford, et al. Influence of Mammographic Parenchymal Pattern in Screening-Detected and Interval Invasive Breast Cancers on Pathologic Features, Mammographic Features, and Patient Survival. Am. J. Roentgenol., 188(3): 676-683, 2007. 10. Boyd, N. F., Guo, H., Martin, L. J., et al. Mammographic density and the risk and detection of breast cancer. N. Engl. J. Med., 356, 227-236, 2007. 11. Warren R. Hormones and mammographic breast density. Maturitas, 49, 67–78, 2004. 12. RadiologyInfo - The radiology information resource for patients http://www.radiologyinfo.org/ 13. Sehgal, C. M., et al. A review of breast ultrasound. Journal of Mammary Gland Biology and Neopasia,11(2), 113-123, 2006. 14. Mueller-Holzner, E. et al., Ultrasound-guided core needle biopsy of the breast: does frozen section give an accurate diagnosis? Breast Cancer Res. Treat., 106(3), 399-406, 2007. 15. Planche, K., Vinnicombe, S., Breast imaging in the new era. Cancer Imaging, 4(2), 39-50, 2004. 16. Orel, S. G., Schnall, M. D., MR imaging of the breast for the detection, diagnosis, staging of breast cancer. Radiology, 220(1), 13-30, 2001. 17. Bolan, P. J., Nelson, M. T., Yee, D., et al. Imaging in breast cancer: magnetic resonance spectroscopy. Breast Cancer Research, 7(4), 149-152, 2005. 18. Orel, S., Who should have breast magnetic resonance imaging evaluation? Journal of Clinical Oncology, 26(5), 703-711, 2008. 19. Gonzalez, E., Grafton, W. D., Morris, D. M., Barr, L. H., Diagnosing breast cancer using frozen section from Tru-cut needle biopsies. Ann. Surg., 202, 696-701, 1985. 20. Houssami, N., Ciatto, S., Ellis, I., Ambrogetti, D., Underestimation of malignancy of breast core-needle biopsy. Cancer, 109(3), 487-495, 2007. 21. Cochran, A. J., Roberts, A. A., Saida, T., The place of lymphatic mapping and sentinel node biopsy in oncology. International Journal of Clinical Oncology 8,139–150, 2003. 22. Gipponi, M., Solari, N., Di Somma, F. C., et al., New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: Review of literature and surgical perspectives. Journal of Surgical Oncology 85, 171–179, 2004. 23. Scoggins, C. R., Chagpar, A. B., Martin, R. C. G., et al., Should sentinel lymph-node biopsy be used routinely for staging melanoma and breast cancers? Nature Clinical Practice Oncology, 2, 448-455, 2005. 24. Moore-Higgs, G. J., Radiation option for early stage breast cancer. Seminar in Oncology Nursing, 22(4), 233-241, 2006. 25. Hortobagyi, A.U. Buzdar, Current status of adjuvant systemic therapy for primary breast cancer: progress and controversy. CA Cancer J. Clin. 45, 199-226, 1995. 26. Fisher, B., et al., Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J. Clin. Oncol. 15(7), 2483-2493, 1997. 27. Decatris, M. P., Sundar, S., O’Byrne, K. J., Platinum-based chemotherapy in metastatic breast cancer: current status. Cancer Treatment Reviews, 30(1), 53-81, 2004. 28. Bender, C. M., et al., Cognitive function and reproductive hormones in adjuvant therapy for breast cancer: a critical review. Journal of Pain and Symptom Management, 21(5), 407-424, 2001. 29. Jemal, A., et al., Cancer statistics. CA: a Cancer Journal for Clinician, 59(4), 225-249, 2009. 30. Hansen, N. M., et al., Manipulation of the primary breast tumor and the incidence of sentinel node metastases from invasive breast cancer. Arch Surg., 139, 634-640, 2004. 31. Altınoğlu E. İ., Adair J, H., Near infrared imaging with nanoparticles. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2(5), 461-477, 2010. 32. Drexler, B., et al., Diaphanography in the diagnosis of breast cancer. Radiology, 157, 41-44, 1985. 33. Ohlsson, B., Gundersen, J., Nilsso, D.-M., Diaphanography: a method for evaluation of the female breast. World Journal of Surgery, 4(6), 701-705, 1980. 34. Profio, A. E., et al., Scientific basis of breast diaphanography. Med. Phys., 16(1), 60-65, 1989. 35. Ntziachristos, V., Chance, B., Probing physiology and molecular function using optical imaging. Breast Cancer Research, 3(1), 41-46, 2001. 36. Leff DR, Warren OJ, Enfield LC, et al. Diffuse optical imaging of the healthy and diseased breast: a systematic review. Breast Cancer Res. Treat. 108, 9-22, 2008. 37. E. Tanaka, S. Ohnishi, R. G. Laurence, H. S. Choi, V. Humblet, J. V. Frangioni, Real-time intraoperative ureteral guidance using invisible near-infrared fluorescence. Journal of Urology, 178, 2197-2202, 2007. 38. Yanagi, Y., et al., Fluorescein angiography-guided indocyanine green angiography for the detection of feeder vessels in subfoveal choroidal neovascularization. Eye, 18, 474-477, 2004. 39. Ferencz, M., et al., Functional assessment of the possible toxicity of indocyanine green dye in macular hole surgery. Am. J. Ophthalmol., 142, 765-770, 2006. 40. J. Li, Z.-G., Lan, M. He, C. You, Assessment of microscope-integrated indocyanine green angiography during intracranial aneurysm surgery: A retrospective study of 120 patients, 57 (4), 453-459, 2009. 41. C. Perlitz, K. Licha, F.-D. Scholle, B. Ebert, M. Bahner, P. Hauff, K. P. Moesta, M. Schirner, Comparison of two tricarbocyanine-based dye for fluorescence optical imaging. Journal of Fluorescence 15, 443-454, 2005. 42. K. Licha, B. Riefke, V. Ntziachristos, A. Becker, B. Chance, W. Semmler, Hyadrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization. Photochemistry and Photobiology, 72, 392-398, 2000. 43. B. Ebert, U. Sukowski, D. Grosenick, H. Wabnitz, K. T. Moesta, K. Licha, A. Becker, W. Semmler, P. M. Schlag, H. Rinneberg, Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments. Journal of Biomedical Optics, 6, 134-140, 2001. 44. Ntziachristos, V., et al., Current MRI and diffuse optical tomography of breast after indocyanine green enhancement. PNAS, 97(6), 2767-2772, 2000.
摘要: 
本研究以自行合成的紅外光螢光物質diglucosamid-SIDAG為顯影劑,增強正常組織、良性異常組織模擬植入物與乳癌組織植入物螢光影像間的對比訊號,並以超音波影像為黃金標準,檢測異常組織的邊界與內部血流量變化情形。
實驗進行包含16隻裸鼠,前後分成5批,其中12隻為實驗組,另外4隻為對照組。在實驗組裸鼠的兩邊體側皮下植入乳癌細胞株(MCF-7 cells)或/及生物凝膠(MatrigelTM),而對照組裸鼠的身上則沒有植入任何物質。先使用高解析超音波針對裸鼠身上之植入物(乳癌細胞株或生物凝膠)做取像的動作,評估其形狀及測量大小,並偵測其有無血流增加;接著在十二小時內,便從所有裸鼠的尾部靜脈注射由本實驗室合成之diglucosamid-SIDAG(50~100ul),利用非侵入式活體影像系統取得從第0到8小時之影像,針對植入物的位置、強度及螢光對時間之曲線變化,進行統計分析,並與超音波檢查的結果作比較。
結果指出,所有生物凝膠植入物的超音波影像呈現扁平和均質的囊性變化 ,並具有明確的邊緣。然而,乳癌細胞株植入物的超音波影像則呈現圓形或橢圓形的外型,葉狀邊緣及部分中央異質性(超過50%乳癌細胞株植入物)。在彩色都普勒影像下,大約20%的乳癌細胞株植入物可偵測到血流增加的現象,但在生物凝膠植入物中均無發現。注射diglucosamid-SIDAG之後老鼠身體的螢光強度大約在注射後一小時達最高峰,隨後逐漸下降。然而,雖然乳癌細胞株的螢光強度亦隨時間逐漸下降,但因其呈現“延遲沖蝕現象”,與正常組織及生物凝膠植入物的發光強度差異或對比值隨時間上升,在第6到第8小時之間達差異或對比值的最大值。在活體螢光影像中,植入之乳癌細胞株的整體偵測率為 88.2% 。
是故以diglucosamid-SIDAG為顯影劑的活體螢光影像,可成為一項對臨床乳癌診斷與治療具潛力的替代方案。

Self-synthesized near-infrared (NIR) fluorescent dye, diglucosamid-SIDAG, was applied to enhance the contrast of fluorescent imaging between normal tissue, benign lesion simulated xenograft and breast cancer tissue xenograft. The high-resolution sonography was referred as gold standard to identify the margin of lesions and investigate the existence of neovascular blood flow inside the lesion.
A total of 16 NU/NU nude mice were enrolled and divided into 5 groups. Twelve of them were implanted with MCF-7 cells (breast cancer cell line)-MatrigelTM mixture and/or pure MatrigelTM subcutaneously, and the other four mice were kept as control group. The morphology and blood flow pattern of all xenografts were inspected by the high resolution sonography. Within 12 hours, the in vivo fluorescent imaging was performed on mice after tail vein injection of diglucosamid-SIDAG from 0 to 8 hours. The location, intensity and time-to-radiance curve from xenografts were analyzed statistically and compared with the sonogram.
All sonogram of the MatrigelTM xenografts appeared flat, homogeneously cystic change with distinct margin. However, the sonogram of MCF-7 xenografts showed round or oval shape, lobular margin with partly central heterogeneity (more than 50% MCF-7 xenografts). Approximately 20% of the MCF-7 xenografts showed increased blood flow under color Doppler imaging, but none of it showed in the MatrigelTM xenografts. The fluorescent intensities of the whole mice reached peak-values about one hour after diglucosamid-SIDAG injection, and faded gradually afterward. However, the MCF-7 xenografts exhibited ‘delayed wash-out phenomenon' with increased radiant difference or ratio compared to both normal tissues and MatrigelTM xenografts, and highlighted between the 6th and 8th hours. The overall detection rate of the MCF-7 xenografts from the in vivo fluorescent imaging was 88.2%.
The in vivo fluorescent imaging with diglucosamid-SIDAG as contrast agent could be a potential alternative option for clinical breast cancer diagnosis and treatment.
URI: http://hdl.handle.net/11455/3939
其他識別: U0005-0702201122071000
Appears in Collections:生醫工程研究所

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