تخمین ضریب کیفیت و تأثیر بیولوژیکی نسبی الکترون‌های گادولینیوم در نوترون درمانی با کمک دیدگاه میکرودوزیمتری

نویسندگان

دانشگاه حکیم سبزواری

چکیده

در این مطالعه تأثیر بیولوژیکی نسبی الکترون‌های اوژه و تبدیل داخلی ناشی از واکنش جذب نوترون حرارتی در گادولینیوم در نوترون درمانی با کمک توابع وزن دهی بیولوژیک با دیدگاه میکرودوزیمتری تخمین زده شده است. با تغییر موقعیت گادولینیوم نسبت به مولکول حاوی DNA، پارامترهای میکرودوزیمتری و توابع احتمال مربوط به انرژی خطی الکترون‌های گادولینیوم در هدف، با کمک بسته DNA ابزار Geant4 و نرم‌افزار تحلیل نتایج ROOT محاسبه شده است. نتایج نشان می‌دهد اگرچه تغییرات تأثیر بیولوژیکی نسبی الکترون‌های گادولینیوم به توزیع متفاوت گادولینیوم نسبت به مولکول حاوی DNA کم است، اما دوز ذخیره‌شده الکترون‌های گادولینیوم شدیداً به توزیع گادولینیوم بستگی دارد. در موردی که گادولینیوم در مرکز مولکول حاوی DNA توزیع شد، متوسط دوز ذخیره‌شده در مولکول حاوی DNA برای یک واکنش جذب نوترون حرارتی در گادولینیوم، ضریب کیفیت تابش و ضریب تأثیر بیولوژیکی با کمک توابع وزن دهی بیولوژیک به ترتیب kGy 85، 10.52 و 2.68 محاسبه شد. مقدار محاسبه‌شده تأثیر بیولوژیکی نسبی الکترون‌های گادولینیوم در این مطالعه با استفاده از تابع وزن دهی بیولوژیک (2.68)، تقریباً معادل تأثیر بیولوژیکی نوترون‌های درمانی است که تحت شرایط مشخص برای تعیین تابع وزن دهی اندازه‌گیری شده بود. اگر اطلاعات دقیقی نسبت به توزیع مکانی گادولینیوم یا تابش کننده‌های الکترون اوژه در سلول داشته باشیم می‌توانیم تخمین بهتری برای تأثیر بیولوژیکی الکترون‌های گادولینیوم یا در حالت کلی الکترون‌های اوژه برسیم.
 

کلیدواژه‌ها


عنوان مقاله [English]

Evaluation of the relative biological effectiveness of the Auger electrons produced during gadolinium neutron capture therapy using microdosimetric approach

نویسندگان [English]

  • Masud Golshani
  • Ali Asghar Mowlavi
  • Behnam Azadegan
چکیده [English]

Determination of the relative biological effectiveness (RBE) of Auger electrons is a challenging task in radiobiology. In this study, we have estimated the RBE of internal conversion (IC) and Auger electrons released during Gadolinium neutron capture reaction (GNCR) by means of biological weighting functions (BWFs) with microdosimetric approach. Regarding the different distribution of Gadolinium (Gd) relative to the DNA as a target, the microdosimetric parameters of the Gd electrons were calculated using the Geant4 Monte Carlo toolkit and ROOT software. Assuming Gd infiltration into the cells and uniform distribution inside the Cell, the lineal energy distribution of Gd electrons in DNA was used instead of the lineal energy distribution of external radiations in the micrometer-diameter targets, which has been conventionally used in the mentioned methods.
The results show that the calculated RBE values of Gd electrons using BWFs (2.68) for the case where Gd distributed at the center of the DNA are approximately equivalent to the RBE value of the therapeutic neutrons, which were measured in the literatures with the same biological conditions. According to the results, although the changes of the RBE of Gd electrons to the different distribution of Gd relative to the DNA are small, the amount of biological dose of the Gd electrons in the DNA is strongly dependent on the Gd distribution. In the case where Gd distributed at the center of DNA, the mean biological dose of Gd electrons in DNA during one GNCR (227.8 kGy.Eq) is large enough for occurring double-strand breaks (DSB) of the DNA. If we have accurate information about the spatial distribution of Gd or Auger-electron emitters inside the cell, by comparing to the results obtained in this study, we can have a better estimation of the RBE of the Gd electrons or in general Auger electrons.
 

کلیدواژه‌ها [English]

  • RBE
  • Auger electrons
  • Biological weighting function
  • Microdosimetric kinetic model
  • GEANT4
[1] Shih, J. L. A., & Brugger, R. M. (1992). Gadolinium as a neutron capture therapy agent. Medical physics, 19(3), 733-744.‌ [2] Miller Jr, G. A., Hertel, N. E., Wehring, B. W., & Horton, J. L. (1993). Gadolinium neutron capture therapy. Nuclear technology,103(3), 320-331.‌ [3] Goorley, T., & Nikjoo, H. (2000). Electron and photon spectra for three gadolinium-based cancer therapy approaches. Radiation research, 154(5), 556-563.‌ [4] Stepanek, J. (2003). Emission spectra of Gadolinium‐158.Medical physics, 30(1), 41-43.‌ [5] Martin, R. F., D'Cunha, G., Pardee, M., & Allen, B. J. (1988). Induction of double-strand breaks following neutron capture by DNA-bound 157Gd. International Journal of Radiation Biology,54(2), 205-208.‌ [6] Kassis, A. I., Fayad, F., Kinsey, B. M., Sastry, K. S. R., Taube, R. A., & Adelstein, S. J. (1987). Radiotoxicity of 125I in mammalian cells. Radiation research, 111(2), 305-318.‌ [7] akrigiorgos, G. M., Kassis, A. I., Baranowska-Kortylewicz, J., McElvany, K. D., Welch, M. J., Sastry, K. S. R., & Adelstein, S. J. (1989). Radiotoxicity of in V79 Cells: A Comparison with.Radiation research, 118(3), 532-544.‌ [8] Narra, V. R., Howell, R. W., Harapanhalli, R. S., Sastry, K. S., & Rao, D. V. (1992). Radiotoxicity of some iodine-123, iodine-125 and iodine-131-labeled compounds in mouse testes: implications for radiopharmaceutical design. Journal of Nuclear Medicine,33(12), 2196-2201.‌. [9] Rao, D., Howell, R., Narra, V., Govelitz, G., & Sastry, K. R. (1989). In-vivo radiotoxicity of DNA-incorporated 125I compared with that of densely ionising alpha-particles. The lancet,334(8664), 650-653.‌ [10] Humm, J. L., Howell, R. W., & Rao, D. V. (1994). Dosimetry of Auger‐electron‐emitting radionuclides: Report No. 3 of AAPM Nuclear Medicine Task Group No. 6. Medical Physics, 21(12), 1901-1915.‌ [11] Valentin, J. (2003). Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR): ICRP Publication 92. Annals of the ICRP, 33(4), 1-121.‌ [12] K. Weyrather, S. Ritter, M. Scholz, G. Kraft, W. (1999). RBE for carbon track-segment irradiation in cell lines of differing repair capacity. International journal of radiation biology, 75(11), 1357-1364.‌ [13] Goodhead, D. T., & Nikjoo, H. (1989). Track structure analysis of ultrasoft X-rays compared to high-and low-LET radiations.International Journal of Radiation Biology, 55(4), 513-529.‌ [14] Lindborg, L., Hultqvist, M., Tedgren, Å. C., & Nikjoo, H. (2013). Lineal energy and radiation quality in radiation therapy: model calculations and comparison with experiment. Physics in Medicine & Biology, 58(10), 3089.‌ [15] Lindborg, L., & Nikjoo, H. (2011). Microdosimetry and radiation quality determinations in radiation protection and radiation therapy. Radiation protection dosimetry, 143(2-4), 402-408.‌ [16] CRU, M. (1983). Report 36. International Commission on Radiation Units and Measurements, Bethesda, MD.‌ [17] Zaider, M., Rossi, B. H. H., & Zaider, M. (1996). Microdosimetry and its Applications. John Libbey..‌ [18] Pihet, P., Menzel, H. G., Schmidt, R., Beauduin, M., & Wambersie, A. (1990). Biological weighting function for RBE specification of neutron therapy beams. Intercomparison of 9 European centres. Radiation Protection Dosimetry, 31(1-4), 437-442.‌ [19] De Nardo, L., Moro, D., Colautti, P., Conte, V., Tornielli, G., & Cuttone, G. (2004). Microdosimetric investigation at the therapeutic proton beam facility of CATANA. Radiation protection dosimetry, 110(1-4), 681-686.‌ [20] Kase, Y., Kanai, T., Matsumoto, Y., Furusawa, Y., Okamoto, H., Asaba, T., ... & Shinoda, H. (2006). Microdosimetric measurements and estimation of human cell survival for heavy-ion beams. Radiation research, 166(4), 629-638.‌ [21] International Commission on Radiation Units and Measurements. (1986). The quality factor in radiation protection. ICRU Report 40.‌ [22] Tilikidis, A., Lind, B., Näfstadius, P., & Brahme, A. (1996). An estimation of the relative biological effectiveness of 50 MV bremsstrahlung beams by microdosimetric techniques. Physics in Medicine & Biology, 41(1), 55.‌ [23] Loncol, T., Cosgrove, V., Denis, J. M., Gueulette, J., Mazal, A., Menzel, H. G & Sabattier, R. (1994). Radiobiological effectiveness of radiation beams with broad LET spectra: microdosimetric analysis using biological weighting functions.Radiation Protection Dosimetry, 52(1-4), 347-352.‌ [24] Y. Hsu, F., J. Tung, C., & E. Watt, D. (2003). Microdosimetric spectra of the THOR neutron beam for boron neutron capture therapy. Radiation protection dosimetry, 104(2), 121-126.‌ [25] Coutrakon, G., Cortese, J., Ghebremedhin, A., Hubbard, J., Johanning, J., Koss, P., ... & Robertson, J. (1997). Microdosimetry spectra of the Loma Linda proton beam and relative biological effectiveness comparisons. Medical Physics,24(9), 1499-1506.‌ [26] Lillhök, J. E., Grindborg, J. E., Lindborg, L., Gudowska, I., Carlsson, G. A., Söderberg, J., ... & Medin, J. (2007). Nanodosimetry in a clinical neutron therapy beam using the variance-covariance method and Monte Carlo simulations.Physics in Medicine & Biology, 52(16), 4953.‌ [27] Salvat, F., Fernández-Varea, J. M., & Sempau, J. (2006, July). PENELOPE-2006: A code system for Monte Carlo simulation of electron and photon transport. In Workshop proceedings (Vol. 4, No. 7).‌ [28] Nikjoo, H., Uehara, S., Emfietzoglou, D., & Cucinotta, F. A. (2006). Track-structure codes in radiation research. Radiation Measurements, 41(9-10), 1052-1074.‌ [29] Incerti, S., Baldacchino, G., Bernal, M., Capra, R., Champion, C., Francis, Z., ... & Nieminen, P. (2010). The geant4-dna project. International Journal of Modeling, Simulation, and Scientific Computing, 1(02), 157-178.‌ [30] Sato, T., Kase, Y., Watanabe, R., Niita, K., & Sihver, L. (2009). Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model. Radiation Research, 171(1), 107-117.‌ [31] Francis, Z., Incerti, S., Ivanchenko, V., Champion, C., Karamitros, M., Bernal, M. A., & El Bitar, Z. (2011). Monte Carlo simulation of energy-deposit clustering for ions of the same LET in liquid water. Physics in Medicine & Biology, 57(1), 209.‌ [32] Burigo, L., Pshenichnov, I., Mishustin, I., & Bleicher, M. (2014). Microdosimetry spectra and RBE of 1H, 4He, 7Li and 12C nuclei in water studied with Geant4. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 320, 89-99.‌ [33] Bernal, M. A., Bordage, M. C., Brown, J. M. C., Davídková, M., Delage, E., El Bitar, Z. & Karamitros, M. (2015). Track structure modeling in liquid water: A review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit. Physica Medica: European Journal of Medical Physics,31(8), 861-874.‌ [34] Allision, J. (2006). Geant4 developments and applications IEEE Transactions on Nuclear Science 53 No. 1 (2006) 270-278.‌ [35] Cerullo, N., Bufalino, D., & Daquino, G. (2009). Progress in the use of gadolinium for NCT. Applied Radiation and Isotopes, 67(7-8), S157-S160.‌ [36] Panijpan, B. (1977). The buoyant density of DNA and the G+ C content. Journal of chemical education, 54(3), 172.‌ [37] Kellerer, A. M. (1971). Considerations on the random traversal of convex bodies and solutions for general cylinders. Radiation Research, 47(2), 359-376. [38] Brun, R., & Rademakers, F. (1997). ROOT—an object oriented data analysis framework. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 389(1-2), 81-86.‌ [39] Kellerer, A. M., & Hahn, K. (1988). The quality factor for neutrons in radiation protection: Physical parameters. Radiation Protection Dosimetry, 23(1-4), 73-78.‌‌ [40] De Stasio, G., Rajesh, D., Ford, J. M., Daniels, M. J., Erhardt, R. J., Frazer, B. H., ... & Fowler, J. F. (2006). Motexafin-gadolinium taken up in vitro by at least 90% of glioblastoma cell nuclei. Clinical cancer research, 12(1), 206-213.‌ [41] Yasui, L. S., Andorf, C., Schneider, L., Kroc, T., Lennox, A., & Saroja, K. R. (2008). Gadolinium neutron capture in glioblastoma multiforme cells. International journal of radiation biology, 84(12), 1130-1139.