THE METHOD OF DIFFUSE OPTICAL SPECTROSCOPY FOR IN VIVO INVESTIGATION OF SPATIAL DISTRIBUTION OF TUMOR-S HYPOXIA ZONES

Анна Владимировна Масленникова; Анна Геннадьевна Орлова; Герман Юрьевич Голубятников; Владислав Антониевич Каменский; Владимир Иванович Плеханов; Алексей Александрович Бабаев; Людмила Борисовна Снопова; Ирина Павловна Иванова; Татьяна Игоревна Пряникова; Наталия Михайловна Шахова; Илья Викторович Турчин

THE METHOD OF DIFFUSE OPTICAL SPECTROSCOPY FOR IN VIVO INVESTIGATION OF SPATIAL DISTRIBUTION OF TUMOR-S HYPOXIA ZONES

Анна Владимировна Масленникова¹, Анна Геннадьевна Орлова², Герман Юрьевич Голубятников³, Владислав Антониевич Каменский⁴, Владимир Иванович Плеханов⁵, Алексей Александрович Бабаев⁶, Людмила Борисовна Снопова⁷, Ирина Павловна Иванова⁸, Татьяна Игоревна Пряникова⁹, Наталия Михайловна Шахова¹⁰, Илья Викторович Турчин¹¹

research article Pages: 38-43

¹ д.м.н., проф. кафедры лучевой диагностики и лучевой терапии, ГОУ ВПО «Нижегородская государственная медицинская академия» Росздрава (НижГМА), науч. сотрудник Учреждения РАН Институт прикладной физики РАН (ИПФ РАН)
² к.б.н., науч. сотрудник, лаборатория биофотоники отдела когерентной оптики, Учреждение РАН ИПФ РАН
³ к.ф.-м.н., ст. науч. сотрудник, отдел микроволновой спектроскопии, Учреждение РАН ИПФ РАН
⁴ к.ф.-м.н., доцент, вед. науч. сотрудник, лаборатория биофо-тоники отдела когерентной оп-тики, Учреждение РАН ИПФ РАН
⁵ вед. технолог, лаборатория биофотоники отдела когерентной оптики, Учреждение РАН ИПФ РАН
⁶ к.б.н., вед. инженер, кафедра иммунологии и молекулярной биологии, ГОУ ВПО «Нижегородский государственный университет им. Н.И. Лобачевского» (ННГУ)
⁷ к.б.н., зав. отделом морфологии, ГОУ ВПО «Нижегородская государственная медицинская академия» Росздрава (НижГМА)
⁸ д.б.н., зав. научной группой физико-химических воздействий, ГОУ ВПО НижГМА Росздрава
⁹ аспирант кафедры биомеди-цины, ГОУ ВПО ННГУ им. Н.И. Лобачевского
¹⁰ д.м.н., вед. науч. сотрудник, лаборатория биофотоники отдела когерентной оптики, Учреждение РАН ИПФ РАН
¹¹ к.ф.-м.н., зав. лабораторией биофотоники отдела когерентной оптики, Учреждение РАН ИПФ РАН

Keywords: tumor-s oxygenation diffuse optical spectroscopy distribution of blood oxygen saturation level immunohistochemical analysis pimonidazole Pliss-s lymph sarcoma

Abstract

Tumor hypoxia is considered to be a key factor of tumor progression and resistance to radiotherapy. Understanding of importance of this physiological parameter for prognosis of treatment outcome stimulated the development of noninvasive techniques for assessing tumor oxygen status. Information about location of zones with different oxygenation is essential for adjustment of optimal spatial distribution of radiation dose. At present work with the purpose of determination of spatial distribution of hypoxic and oxygenated tumor regions the method of diffuse optical spectroscopy (DOS) was used. This method allows estimation of concentrations of oxygenated and deoxygenated hemoglobin, and, consequently, calculation of blood oxygen saturation level. For determination of spatial distribution of this chromophores, laser scanning in several wavelengths was used. As a method of verification we utilized immunohistochemical analysis with exogenous hypoxia marker - pimonidazole. Experiments were performed using Pliss-s lymph sarcoma model. It has been demonstrated that DOS method allows recognizing of the heterogeneity of tissue chromophores content. DOT images of the central part of Pliss-s lymph sarcoma demonstrated decreased concentration of oxygenated hemoglobin, the increased concentration of deoxygenated hemoglobin and substantial decrease of oxygen saturation as compared with the external part. As it has been shown by immunohistochemical analysis, the central zone of the tumor, in contrast to the periphery, is hypoxic. Thus, immunohistochemical investigation confirmed the DOS results. This method can be promising tool for estimation of the efficacy of radiomodifiers, chemotherapeutic agents and anti-angiogenesis pharmaceuticals.

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Масленникова А.В., Орлова А.Г., Голубятников Г.Ю., Каменский В.А., Плеханов В.И., Бабаев А.А., Снопова Л.Б., Иванова И.П., Пряникова Т.И., Шахова Н.М., Турчин И.В. МЕТОД ОПТИЧЕСКОЙ ДИФФУЗИОННОЙ СПЕКТРОСКОПИИ ДЛЯ IN VIVO ИССЛЕДОВАНИЯ ПРОСТРАНСТВЕННОГО РАСПРЕДЕЛЕНИЯ ЗОН ГИПОКСИИ В ТКАНИ ОПУХОЛИ // Технологии живых систем. 2011. № 2. С. 38–43.

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[1] Eriksen J. E., Horsman M.R. Tumor hypoxia - a characteristic feature with a complex molecular background // Radiotherapy and Oncology. 2006. V. 81. № 2. P. 119-121.

[2] Vaupel P. Hypoxia and Aggressive Tumor Phenotype: Implications for Therapy and Prognosis // The Oncologist. 2008. V. 13. Suppl. 3. P. 21-26.

[3] Horsman M. R., Overgaard J. The oxygen effect and tumour microenvironment. In: Steel G. G., ed. Basic clinical radiobiology. London: Arnold. 2002. P. 58 - 168.

[4] Serganova I., Humm J., Ling C., Blasberg R. Tumor Hypoxia Imaging // Clinical Cancer Research. 2006. V. 12. № 18. P. 5260-5264.

[5] Davda S., Bezabeh T. Advances in methods for assessing tumor hypoxia in vivo: implications for treatment planning // Cancer and Metastasis Reviews. 2006. V. 25. № 3. P. 469-480.

[6] Cerussi A., Hsiang D., Shah N., Mehta R., Durkin A., Butler J., and Tromberg B. J. Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy // PNAS. 2007. V. 104. № 10. P. 4014-4019.

[7] Brown J. Q., Wilke L. G., Geradts J., Kennedy S. A., Palmer G. M., Ramanujam N. Quantitative Optical Spectroscopy: A Robust Tool for Direct Measurement of Breast Cancer Vascular Oxygenation and Total Hemoglobin Content In vivo // Cancer Research. 2009. V. 69 № 7. P. 2919 - 2926.

[8] Orlova A. G., Turchin I. V., Plehanov V. I., Shakhova N. M., Fiks I. I., Kleshnin M. I., Konuchenko N. Yu., Kamensky V. A. Frequency-domain diffuse optical tomography with single source-detector pair for breast cancer detection // Laser Physics Letters. 2008. V. 5. № 4. P. 321-327.

[9] McBride T. O., Pogue B. W., Poplack S., Soho S., Wells W.A., Jiang S., Osterberg U.L., Paulsen K.D. Multispectral near-infrared tomography: a case study in compensating for water and lipid content in hemoglobin imaging of the breast // Journal of Biomedical Optics. 2002. V. 7. № 1. P. 72-79.

[10] Yaromina A., Zips D., Thames H., Eicheler W., Krause M., Rosner A., Haase M., Petersen C., Raleigh J., Quennet V. Pimonidazole labelling and response to fractionated irradiation of five human squamous cell carcinoma (hSCC) lines in nude mice: The need for a multivariative approach in biomarker studies // Radiotherapy and Oncology. 2006. V. 81. № 2. P. 122-129.

[11] Ljungkvist A. S., Bussink J., Kaanders J. H., Wiedenmann N. E., Vlasman R., van der Kogel A. J. Dynamics of hypoxia, proliferation and apoptosis after irradiation in a murine tumor model // Radiat Res. 2006. V. 165. P. 326-336.

[12] Grosu A. L., Piert M., Weber W. A., Jeremic B., Picchio M., Schratzenstaller U., Zimmermann F. B., Schwaiger M., Molls M. Positron emission tomography for radiation treatment planning // Strahlenther Onkol. 2005. V. 181. № 8.
P. 483-499.

[13] Prabhakar R., Jagadesan P., Rath G. K. An insight into PET-CT based radiotherapy treatment planning // Cancer Therapy. 2007. V. 5. P. 519-524.

[14] Boas D. A., Brooks D. H., Miller E. L., DiMarzio C.A., Kilmer M., Gaudette R. J., Zhang Q. Imaging the body with diffuse optical tomography // IEEE Signal Processing Magazine. 2001.
P. 51-75.

[15] Torricelli A., Spinelli L., Pifferi A., Taroni P., Cubeddu R., Danesini G. Use of a nonlinear perturbation approach for in vivo breast lesion characterization by multiwavelength time-resolved optical mammography // Optics Express. 2003. V. 11. № 8. P. 853-867.

[16] Saxena V., Gonzalez-Gomez I., Laug W.E. A noninvasive multimodal technique to monitor brain tumor vascularization. Physics in Medicine and Biology. 2007. V. 52. № 17. P. 5295-5308.

[17] Pham T. H., Hornung R., Berns M. W., Tadir Y., Tromberg B. J. Monitoring Tumor Response During Photodynamic Therapy Using Nearinfrared Photon-migration Spectroscopy // Photochemistry and Photobiology. 2001. V. 73. № 6. P. 669-677.

[18] Jain R. K. Determinants of tumor blood flow: a review // Cancer Res. 1988. V. 48. P. 2641-2658.

[19] Padera T. P., Stoll B. R., Tooredman J. B., Capen D., di Tomaso E., Jain R. K. Pathology: cancer cells compress intratumour vessels // Nature. 2004. V. 427. P. 695.

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