The calculation of internal irradiation of nano-, micro- and macro-biostructures by electrons, beta particles and quantum radiation of different energy for the development and research of new radiopharmaceuticals in nuclear medicine

«Radiation and Risk», 2015, vol. 24, No. 1, pp.35-60

Authors

Степаненко В.Ф. – зав. лаб., д.б.н., проф. A. Tsyb MRRC, Obninsk. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: +7 (484) 399-70-02; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Yaskova E.K. – Lead. Researcher, C. Sc., Biol., A. Tsyb MRRC, Obninsk.
Belukha I.G. – Senior Researcher, C. Sc., Biol., A. Tsyb MRRC, Obninsk.
Petriev V.M. – Lead. Researcher, D.Sc., Biol., A. Tsyb MRRC, Obninsk.
Skvortsov V.G. – Head of Lab, C. Sc., Biol., A. Tsyb MRRC, Obninsk.
Kolyzhenkov T.V. – Senior Researcher, C. Sc., Biol., A. Tsyb MRRC, Obninsk.
Petukhov A.D. – Researcher, A. Tsyb MRRC, Obninsk.
Dubov D.V. – Senior Researcher, C. Sc., Biol., A. Tsyb MRRC, Obninsk.

Abstract

The universal approach for calculations of absorbed doses of internal exposure of nano-, micro- and macro- biostructures by electrons, beta particles and quantum radiation in a wide energy range, almost completely covering the energy range of radiation from radionuclides used in experimental and clinical nuclear medicine, is developed. The polynomial functions that describe the distribution of absorbed energy in biological tissue around point isotropic sources of electrons and quantum radiation in a wide energy range: from 0.1 keV to 10 MeV for electrons and from 10 keV to 4 MeV for quantum radiation, are presented. Integration of these functions over the volume of biostructures – «sources» and «targets» allows to carry out calculations of distribution of absorbed energy in a case of internal exposure of nano-, micro- and macro-biostructures by electrons, beta particles, and gamma quanta, which emitted by different radionuclides used in experimental and clinical nuclear medicine. The developed method was applied in order to calculate the distribution of absorbed dose in the volume of transplantable Erlikh-carcinoma (radius of tumor is equal to 0.8 cm), which irradiated by 153Sm-albumin microspheres radiopharmaceutics. The significant non-uniformity of dose distribution within tumor’s volume in case of location of the radiopharmaceutics in the center of the tumor was demonstrated. The possibility of reducing the dose variability was evaluated. The obtained data show, that proper choice of the localization of the radiopharmaceutics in the tumour’s volume is essential in order to reach the maximum radiation exposure of all tumor cells. It was demonstrated in a case of 153Sm the distribution of the radiation source on the periphery of the tumor helps to reduce essentially the nonhomogeneity of dose distribution within the tumor in comparison with the case of the source location in the central part of the tumor. The developed method was applied for estimations of exposure of subcellular microstructures (nucleus, cytoplasm and cell membrane) in a case of internal irradiation by 51Cr, 67Ga, 111In, 123I, 125I, 77Br, which are cascade emitters of Auger electrons and Coster-Kronig electrons. These emitters are able to produce high local ionization density in biostructures of nanometric dimensions. As a result, the following Auger emitters were selected as promising radionuclides for the development of radiopharmaceuticals, which are able to produce selective radiation effects on the DNA of cells: 123I, 125I, 77Br, 111In. It was also shown that at each act of photoelectric effect on attached stable atoms of iodine or bromine to the DNA, as well as on native phosphorus of DNA, the cascade emission of low-energy electrons resulted in absorption of 0.3-0.8 keV a volume with a diameter of about 100 nanometers around the atom. This energy is comparable to the value of the absorbed energy in a case of radioactive 125I decay. Results of estimates of expected values of RBE at the photoelectric effect on the atoms of iodine or bromine attached to the DNA of cells of melanoma B16 provides the rationale for further studies of this phenomenon to develop the methods of binary radiotherapy, using the photoelectric effect on heavy atoms (such as iodine or bromine) attached to the DNA of tumor cells.

Key words
dosimetry of internal irradiation, nano-dosimetry, microdosimetry, nuclear medicine, conversion electrons, Auger electrons, Coster-Kronig electrons, beta-particles, characteristic quantum radiation, gamma-rays, radionuclides, radiopharmaceuticals, albumin microspheres, DNA, iododeoxyuridine, bromodeoxyuridine.

References

Briemeister J.F. MCNP – a general Monte-Carlo n-particle transport code. Version 4B. Los Alamos, 1997.

2. Report on the Task Group on Reference Man. ICRP Publication no. 23. Chapter 2. Elsevier Ltd, 1975, рp. 335-365.

3. Bolch W.E., Eckerman K.F., Sgouros G., Thomas R. MIRD Pamphlet no. 21: A Generalized Schema for Radiopharmaceutical Dosimetry-Standardization of Nomenclature. J. Nucl. Med., 2009, vol. 50, no. 11, pp. 477-484.

4. Stepanenko V.F. Radiobiologicheskaja znachimost' elektronov malyh jenergij pri vnutrennem gamma-elektronnom obluchenii (radiacionnye aspekty). Diss. dokt. biol. nauk. [Radiobiological significance of low-energy electrons at internal gamma-electron irradiation (radiation aspects). Dr. biol. sci. diss.]. Obninsk, 1978. 219 p.

5. Stepanenko V.F., Yaskova E.K., Belukha I.G., Dubov D.V. Raschet raspredeleniya pogloshchennoy energii v nano-, mikro- i makro-biostrukturakh, modeliruemykh sfericheskimi ob"emami, pri vnutrennem obluchenii elektronami i beta-chastitsami (sphere-electron) [The calculation of distribution of absorbed energy in nano-, micro- and macro-biostructures, simulated by spherical volumes, at internal irradiation by electrons and beta particles (sphere-electron)]. Author's copyright certificate no. 2012619812 on the state registration of the computer program. Moscow, Federal Service on Intellectual Property and Patents (Rospatent), 2012.

6. Stepanenko V.F., Belukha I.G., Yaskova E.K., Dubov D.V. Raschet raspredeleniya pogloshchennoy energii v nano-, mikro- i makro-biostrukturakh, modeliruemykh ob"emami v vide sloya konechnoy tolshchiny, pri vnutrennem obluchenii elektronami i beta-chastitsami (layer-electron) [The calculation of distribution of absorbed energy in nano-, micro- and macro-biostructures, simulated by volumes in a layer of finite thickness, at internal irradiation by electrons and beta particles (layer-electron)]. Author's copyright certificate no. 2013610046 on the state registration of the computer program. Moscow, Federal Service on Intellectual Property and Patents (Rospatent), 2013.

7. Stepanenko V.F., Yaskova E.K., Belukha I.G., Dubov D.V. Raschet raspredeleniya pogloshchennoy energii v biostrukturakh, modeliruemykh sfericheskimi ob"emami, pri vnutrennem obluchenii gamma-kvantami (sphere-gamma) [The calculation of distribution of absorbed energy in the biostructures, simulated by spherical volumes, at internal irradiation by gamma-quanta (sphere-gamma)]. Author's copyright certificate no. 2013618419 on the state registration of the computer program. Moscow, Federal Service on Intellectual Property and Patents (Rospatent), 2013.

8. Stepanenko V.F., Belukha I.G., Yaskova E.K., Dubov D.V. Raschet raspredeleniya pogloshchennoy energii v biostrukturakh, modeliruemykh ob"emami v vide sloev, pri vnutrennem obluchenii gamma-kvantami (layer-gamma) [The calculation of distribution of absorbed energy in the biostructures, simulated volumes in the form of layers, at internal irradiation by gamma-quanta (layer-gamma)]. Author’s copyright certificate no. 2013619974 on the state registration of the computer program. Moscow, Federal Service on Intellectual Property and Patents (Rospatent), 2013.

9. Skvortsov V.G., Stepanenko V.F., Petriev V.M., Yaskova E.K., Kryukova I.G., Sokolov V.A., Borysheva N.B., Shiriaeva V.K., Orlenko S.P., Khailov A.M., Tsyb A.F. Farmakokineticheskie i dozimetricheskie kharakteristiki novogo radiofarmpreparata 103Pd mikrosfery al'bumina [Pharmacokinetic and dosimetric characteristics of a new radiopharmaceutical 103Pd microspheres of albumin]. Radiatsionnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2010, vol. 15, no. 6, pp. 703-711.

10. Stepanenko V.F., Petriev V.M., Orlov M.Yu., Kryukova I.G., Sokolov V.A., Tsyb A.F. Dozy vnutrennego oblucheniya organizma v eksperimental'nykh issledovaniyakh novogo preparata na osnove 103Pd i mikrosfer al'bumina dlya radionuklidnoy terapii [The internal doses of the organism in experimental studies of a new radiopharmaceutics on the basis of 103Pd and albumin microspheres for radionuclide therapy]. Trudy regional'nogo konkursa nauchnykh proektov v oblasti estestvennykh nauk [Issues of the regional competition of scientific projects in the field of natural sciences]. Kaluga, KSC AKO RFBR, vol. 15, pp. 171-180.

11. Orlov M.Yu., Stepanenko V.F., Petriev V.M., Skvortsov V.G., Borysheva N.B., Volkov D.M. Osobennosti raspredeleniya dozy oblucheniya biologicheskikh tkaney posle vvedeniya v opukhol' al'buminovykh mikrosfer s 103Pd [Features of the distribution of doses in biological tissues after injection into the tumor albumin microspheres with 103Pd]. Meditsinskaya fizika – Medical Physics, 2011, vol. 51, no. 3, pp. 47-51.

12. Yaskova E.K., Stepanenko V.F., Petriev V.M., Skvortsov V.G., Sokolov V.A., Kryukova I.G., Shiriaeva V.K., Belorukova N.V., Kalshnikova E.E., Dubov D.V., Tsyb A.F. Otsenka pogloshchennykh doz vnutrennego oblucheniya laboratornykh zhivotnykh pri vvedenii radiofarmpreparatov, mechenykh 99mTc i 188Re [Evaluation of absorbed doses of internal exposure of laboratory animals at the injection of radiophar-maceuticals labeled by 99mTc and 188Re]. Radiatsiya i risk – Radiation and Risk, 2010, vol. 19, no. 4, pp. 50-57.

13. Dillman L.T., Von der Lage. Radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation. MIRD Pamphlet no. 10. NY, MIRD, 1975. 117 p.

14. Stepanek J., Larsson B., Weinreich R. Auger-electron spectra of radionuclides for therapy and diagnostics. Acta Oncologica, 1996, vol. 35, no. 7, pp. 863-868.

15. Stepanek J., Ilvonen S.A., Kuronen A.A., Lampinen I.S., Savolainen E., Valimaki P.J. Radiation spectra of 111In, 113mIn, 114mIn. Acta Oncologica, 2000, vol. 39, no. 6, pp. 667-671.

16. Lee B.Q., Kibedi T., Stuchbery A.E., Robertson K.A. Atomic radiations in the decay of medical radioisotopes: a physics perspective. Computation and Mathematical Methods in Medicine, Hindawi Publishing Corporation, 2012, vol. (2012). Article ID 651475. 14 p.

17. Stepanenko V.F., Petriev V.M., Orlov M.Yu., Skvortsov V.G., Belukha I.G., Dubov D.V., Yaskova E.K., Tsyb A.F. Kaskadnye izluchateli elektronov maloy energii dlya razrabotki novykh terapevticheskikh radiofarmpreparatov [Cascade emitters of low-energy electron for the development of new therapeutic radiopharmaceuticals]. Meditsinskaya fizika – Medical Physics, 2013, vol. 58, no. 2, pp. 15-19.

18. Charlton D.E., Humm J.L. A method of calculating initial DNA strand breakage following the decay of incorporated 125I. Int. J. Radiat. Biol. 1988. V. 53. P. 353-365.

19. Datta K., Weinfeld M., Neumann R.D. Determination and analysis of site-specific 125I decay-induced DNA double-strand break end-group structures. Radiation Research. 2007. V. 167. P. 152-166.

20. Stepanenko V.F., Belukha I.G., Dubov D.V., Yaskova E.K. Nanodozimetricheskoe obosnovanie izbiratel'nogo radiatsionnogo vozdeystviya na khromosomy kaskadnymi izluchatelyami elektronov maloy energii [Nanodosimetry rationale of selective irradiation of chromosomes by cascade emitters of low-energy electrons]. Meditsinskaya radiologiya i radiatsionnaya bezopasnost' – Medical Radiology and Radiation Safety, 2012, vol. 57, no. 6, pp. 5-8.

21. Stepanenko V.F., Belukha I.G., Dubov D.V., Yaskova E.K., Tsyb A.F. Nanodozimetricheskoe obosnovanie povysheniya biologicheskoy effektivnosti nizkoenergetichnogo gamma izlucheniya s terapevticheskimi tselyami [Nanodosimetry rationale of increasing the biological effectiveness of low-energy gamma radiation for therapeutic purposes]. Sbornik statey Chetvertoy Mezhdunarodnoy nauchno-prakticheskoy konferentsii «Vysokie tekhnologii, fundamental'nye i prikladnye issledovaniya v fiziologii, meditsine, farmakologii» [Issues of the Fourth International scientific-practical conference «High technologies, fundamental and applied research in physiology, medicine, pharmacology»]. Saint-Petersburg, Polytechnical University, 2012, vol. 1, pp. 118-120.

22. Sastry R.S.R. Biological effects of the Auger emitter 125I: a review. Report no. 1 of AAPM Nuclear Medicine Task Group no. 6. Med. Phys., 1992, vol. 19, pp. 1361-1370.

Full-text article (in Russian)