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Issues journals
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 2
Hyperthermia in Conservative and Palliative Treatment
of Oncological Patients. Part II. Whole Body Hyperthermia
O.K. Kurpeshev1, J. Van der Zee2
1Siberian Scientific Research Institute of Hyperthermia, Novosibirsk, Russia
2Erasmus Medical Centre, Cancer Institute, Rotterdam, The Netherlands
Contact person: Orazakhmet Kurpeshev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
CONTENTS
The analysis of the results of the use of whole-body hyperthermia (WBH) in patients with locally advanced, recurrent and / or metastatic tumors, which, as a rule, are radio- and chemo-resistant. Most patients were incurable, in connection with which the treatment was mainly carried out with a palliative purpose. The analysis showed that the method alone or in combination with chemo- and radiation therapy has pronounced direct and palliative effects, in some cases it provides long-term control. However, WBH can have side effects. This necessitates further improvement of the method, development of a set of preventive measures, as well as improvement of equipment for heating and thermometry.
AbbREVIATIONS
BrCa – Breast cancer
CE – Clinical effect
CR – complete response
CeCa – cervical cancer
CRCa – colo-rectal cancer
CT – chemotherapy
ECWBH – extracorporal WBH
HIPCT – hyperthermic intraperitoneal CT
IR – infrared radiation
IRWBH – IR whole body hyperthermia
IT – immunotherapy
LA – locally advanced
LCa – Lung cancer
LC – local control
ML – malignant limphomas
MМ – malignant mesetelioma
MSTDP – median survival time to disease progression
MST – multi-step therapy
MTS – metastases
HL – Hodgkin’s lymphoma
NSCLC – non small cell lung cancer
RT – radiation therapy
OR – objective response
OS – overall survival
OsSa – osteosarcoma
OvCa – ovarian cancer
PCa – pancreatic Cancer
PE – palliative effect
PR – partial response
RF – radiofreqency
RFWBH – radiofrequency WBH
SD – stabilization disease
SCLC – small cell lung cancer
STS – soft tissue sarcoma
TBRT – total body RT
TTD – tumor total dose
WBH – whole body hyperthermia
Keywords: general hyperthermia, palliative therapy, chemotherapy, radiation therapy, review
For citation: Kurpeshev OK, Van der Zee J. Hyperthermia in conservative and palliative treatment of oncological patients. Part ii. Whole body hyperthermia. Medical Radiology and Radiation Safety. 2022;67(2):43-58. doi: 10.33266/1024-6177-2022-67-2-43-58
References
1. Coley W.B. The Treatment of Malignant Tumors by Repeated Inoculations of Erysipelas, with a Report of Ten Original Cases. Am. J. Med. Sci. 1893;105:487-511.
2. Busch W. On the Influence Which more Violent Erysipeline Sometimes Exerts on Organized Neoplasms. Negotiations of the Natural History Association of the Prussian Rhineland and Westphalia. 1866;23:28-30 (German). [Busch W. Uber Den Einfluss, Welchen Heftigere Erysipelin Zuweilig auf Organisierte Neubildungen Ausüben // Verhandlugen des Naturhistorischen Vereines der Preussischen Rheinlande und Westphalens. 1866. No. 23. P. 28-30].
3. Ismail-zade R.S. Obshchaya Upravlyayemaya Gipertermiya v Kompleksnom Lechenii Daleko Zashedshikh i Refrakternykh Form Zlokachestvennykh Opukholey u Detey = Total Controlled Hyperthermia in the Complex Treatment of Advanced and Refractory Forms of Malignant Tumors in Children. Extended Abstract of Doctor’s thesis in Medicine. Minsk Publ., 2008.42 p. (In Russian). [Исмаил-заде Р.С. Общая управляемая гипертермия в комплексном лечении далеко зашедших и рефрактерных форм злокачественных опухолей у детей: Автореф. дис. ... докт. мед. наук. Минск, 2008. 42 с.].
4. Karev I.D., Rodina A.A., Gut N.V. Obshchaya Vysokotemperaturnaya Gipertermiya v Lechenii Disseminirovannykh Khimiorezistentnykh Opukhole = General High-Temperature Hyperthermia in the Treatment of Disseminated Chemoresistant Tumors. Materialy III Syezda Onkologov i Radiologov SNG = Materials of the III Congress of Oncologists and Radiologists of the CNG. Minsk, 25-28 May, 2004. Part 1. Minsk Publ., 2004. P. 146-149. (In Russian). [Карев И.Д., Родина А.А., Гут Н.В. Общая высокотемпературная гипертермия в лечении диссеминированных химиорезистентных опухолей // Материалы III съезда онкологов и радиологов СНГ. Минск, 25-28 мая 2004. Ч. 1. Минск, 2004. С. 146-149].
5. Mardynskiy Yu.S., Kurpeshev O.K., Pavlov V.V., Smirnova I.A. Reactions and Complications after General Electromagnetic Hyperthermia of Tumors at the “Yachta-5” Device. Rossiyskiy Onkologicheskiy Zhurnal = Russian Journal of Oncolo-
gy. 2001;6:4-8. (In Russian). [Мардынский Ю.С., Курпе-
шев О.К., Павлов В.В., Смирнова И.А. Реакции и осложнения после общей электромагнитной гипертермии опухолей на установке “Яхта-5” // Российский Онкологический журнал. 2001. № 6. С. 4-8].
6. Kurpeshev O. Radiofrequency Whole Body Hyperthermia (WBHT) in Cancer Treatment. 28th Annual Meeting Society for Thermal Medicine, New Orleans, USA. 2011. Abstract 0081. New Orleans, 2011.
7. Suvernev A.V., Ivanov G.V. Intensivnoye Teplolecheniye = Intensive Heat Therapy. Novosibirsk, Akademicheskoye Izd-vo “Geo” Publ., 2014. 106 p. (In Russian). [Сувернев А.В., Иванов Г.В. Интенсивное теплолечение. Новосибирск: Академическое изд-во “Гео”, 2014. 106 с.].
8. Van der Zee J., Faithfull N.S., van Rhoon G.C., Reinhold H.S. Whole Body Hyperthermia as a Treatment Modality. Physics and Technology of Hyperthermia. Ed. Field S.B., Franconi C. Springer, Dordrecht, 1987. P. 420-440. DOI https://doi.org/10.1007/978-94-009-3597-6.
9. Hildebrandt B., Hegewisch-Becker S., Kerner T., Nierhaus A., Bakhshandeh-Bath A., Janni W., Zumschlinge R., Sommer H., Riess H., Wust P. Current Status of Radiant Whole-Body Hyperthermia at Temperatures >41.5 o C and Practical Guidelines for the Treatment of Adults. The German ‘Interdisciplinary Working Group on Hyperthermia. Int. J. Hyperthermia. 2005;21;2:169–183. DOI: 10.1080/02656730400003401.
10. Bull J.M.C., Scott G.L., Strebel F.R., Nagle V.L., Oliver D., Redwine M., Rowe R.W., Ahn C.W., Koch S.M. Fever-Range Whole-Body Thermal Therapy Combined with Cisplatin, Gemcitabine, and Daily Interferon-Alpha: a Description of a Phase I-II Protocol. Int. J. Hyperthermia. 2008;24;8:649–662.
11. Lassche G., Crezee J., Van Herpen C.M.L. Whole-Body Hyperthermia in Combination with Systemic Therapy in Advanced Solid Malignancies. Critical Reviews in Oncology/Hematology. 2019;139:67-74. https://doi.org/10.1016/j.critrevonc.2019.04.023.
12. Robins H.I., Longo W.L., Steeves R.A. A Pilot Study of Whole Body Hyperthermia and Local Irradiation for Advanced Non-Small Cell Lung Cancer Confined TO THE Thorax. Int. J. of Rad. Oncol. Biol. Phys. 1988;15:2:427-431.
13. Robins H.I., Longo W.L., Lagoni R.K., Neville A.J., Hugander A., Schmitt C.L., Riggs C. A Phase I Trial of Lonidamine with Whole Body Hyperthermia in Advanced Cancer. Cancer Res. 1988;43:6587–6592.
14. Robins H.I., Sielaff K.M., Storer B., Hawkins M.J., Borden E.C. Phase I Trial of Human Lymphoblastoid Interferon with Whole Body Hyperthermia in Advanced Cancer. Cancer Res. 1989;49;6:1609-15.
15. Takeuchi T., Takeuchi A., Yokoyama M. Clinical Experiences of Far-Infrared Whole-Body Hyperthermia by the Use of rhd2002. Hyperthermic Oncol. 7th Proceed. Int. Congr. Abstracts. Roma. 1996;2:272-273.
16. Larkin J.M.A. Clinical Investigation of Total-Body Hyperthermia as Cancer Therapy. Cancer Research. 1979;39:2252-2254.
17. Maeta M., Koga S., Wada J., Yokoyama M., Kato N., Kawahara H., Sakai T., Hino M., Ono T., Yuasa K. Clinical Evaluation of Total-Body Hyperthermia Combined with Anticancer Chemotherapy for Far-Advanced Miscellaneous Cancer in Japan. Cancer. 1987;59;6:1101-1106. DOI: 10.1002/1097-0142(19870315)59:6<1101::aid-cncr2820
590610>3.0.co;2-g.
18. Robins H.I., Longo W.L., Steeves R.A. Cohen J.D., Schmitt C.L., Neville A.J., O’Keefe S., Lagoni R., Riggs C. Adjunctive Therapy (Whole Body Hyperthermia Versus Lonidamine) to Total Body Irradiation for the Treatment of Favorable B-Cell Neoplasms: A Report on Two Pilot Clinical Trials and Laboratory Investigations. Int. J. Radiat. Oncol. Biol. Phys. 1990;18:909–920. DOI: 10.1016/0360-3016(90)90416.
19. Bull J.M., Cronau L.H., Newman B.M., Jabboury K., Allen S.J., Ohno S., Smith T., Tonnesen A.S. Chemotherapy Resistant Sarcoma Treated with Whole Body Hyperthermia (WBH) Combined with 1-3-Bis(2-Chloroethyl)-1-Nitrosourea (BCNU). Int. J. Hyperthermia. 1992;8;3:297-304.
20. Robins H.I., Cohen J.D., Schmitt C.L., Tutsch K.D., Feierabend C., Arzoomanian R.Z., Alberti D., d’Oleire F., Longo W., Heiss C. Phase I clinical trial of carboplatin and 41.8 °C whole-body hyperthermia in cancer patients. J. Clin. Oncol. 1993;9:1787–1794. DOI: 10.1200/JCO.1993.11.9.1787. PMID: 8355046.
21. Wiedemann G.J., d’Oleire F., Erdmute K.E., Eleftheriadis S., Bucsky P., Feddersen S., Kiouche M., Geisler J., Mentzel M., Schmucker P., Feyerabend T., Weiss C., Wagner T. Ifosfamide and Carboplatin Combined with 41.8 °C Whole-Body Hyperthermia in Patients with Refractory Sarcoma and Malignant Teratoma. Cancer Research. 1994;54:5346-5350.
22. Wiedemann G.J., Robins H.I., Gutsche S., Mentzel M., Deeken M., Katschinski D.M., Eleftheriadis S., Crahe R., Weiss C., Storer B., Wagner T. Ifosfamide, Carboplatin and Etoposide (ICE) Combined with 41.8 C Whole Body Hyperthermia in Patients with Refractory Sarcoma. Eur. J. Cancer. 1996;32;5:888-892. DOI: 10.1016/0959-8049(95)00622-2.
23. Robins H.I., Rushing D., Kutz M., Tutsch K.D., Tiggelaar C.L., Paul D., Spriggs D., Kraemer C., Gillis W., Feierabend C., Arzoomanian R.Z., Longo W., Alberti D., d’Oleire F., Qu R.P., Wilding G., Stewart J.A. Phase I Clinical Trial of Melphalan and 41.8 °C Whole-Body Hyperthermia in Cancer Patients. J. Clin. Oncol. 1997;15:158–164. DOI: 10.1200/JCO.1997.15.1.158. PMID: 8996137.
24. Robins H.I., Katschinski D.M., Longo W., Grosen E., Wilding G., Gillis W., Kraemer C., Tiggelaar C.L., Rushing D., Stewart J.A., Spriggs D., Love R., Arzoomanian R.Z., Feierabend C., Alberti D., Morgan K., Simon K., d’Oleire F. A Pilot Study of Melphalan, Tumor Necrosis Factor-α and 41.8 ° C Whole-Body Hyperthermia. Cancer Chemother. Pharmacol. 1999;
43:409-414.
25. Gruber Y., Hegewisch-Becker S., Bakshandeh-Bath A., Sommer H., Hoffmann R., Hossfeld D.K. Whole-Body Hyperthermia at 41.8 °C Combined with Ifosfamide and Carboplatin in Relapsed Ovarian Carcinoma Pretreated with a Platin-Contai-
ning Regimen. Ann. Oncol. 2000;11:377.
26. Bremer K., Meyer A., Lohmann R. Pilot Study of Whole-Body Hyperthermia Combined with Chemotherapy in Patients with Metastasised Pretreated Progressive Breast, Ovarian, and Colorectal Carcinomas. Tumor Diagn. & Ther. 2001;22:115-120.
27. Westermann A.M., Grosen E.A., Katschinski D.M., Jäger D., Rietbroek R., Schink J.C., Tiggelaar C.L., Jäger E. A Pilot Study of Whole Body Hyperthermia and Carboplatin in Platinum-Resistant Ovarian Cancer. Eur. J. Cancer. 2001;37;9:1111–1117.
28. Strobl B, Janni W, Rjosk D, Rack BK, Kornya L, Bakhshandeh-Bath A, Hegewisch-Becker S, Hildebrandt B, Harald L, Sommer I. Chemotherapy with Carboplatin/Ifosfamide Combined with Whole Body Hyperthermia in Recurrent Ovarian Cancer—Results of a Phase II Study (Dolphin-1-Study). Proc. Am. Soc. Clin. Oncol. 2002;19:A2523.
29. Bakhshandeh A., Bruns I., Traynor A., Robins H.I., Eberhardt K., Demedts A., Kaukel E., Koschel G., Gatzemeier U., Kohlmann T., Dalhoff K., Ehlers E.M., Gruber Y., Zumschlinge R., Hegewisch-Becker S., Peters S.O., Wiedemann G.J. Ifosfamide, Carboplatin and Etoposide Combined with 41.8 °C Whole Body Hyperthermia for Malignant Pleural Mesothelioma. Lung Cancer. 2003;39;3:339–345.
30. Westermann A.M., Wiedemann G.J., Jager E., Jager D., Katschinski D.M., Knuthc A., Vörde sive Vörding P.Z., Van Dijk J.D.P., Finet J., Neumann A., Longo W., Bakhshandeh A., Tiggelaar C.L., Gillis W., Bailey H., Peters S.O., Robins H.I. A Systemic Hyperthermia Oncologic Working Group Trial. Ifosfamide, Carboplatin, and Etoposide Combined with 41.8 Degrees C Whole-Body Hyperthermia for Metastatic Soft Tissue Sarcoma. Oncology. 2003;64;4:312-321. DOI: 10.1159/000070287.
31. Hegewisch-Becker S., Gruber Y., Corovic A., Pichlmeier U., Atanackovic D., Nierhaus A., Hossfeld D.K. Whole Body Hyperthermia (41.8 °C) Combined with Bimonthly Oxaliplatin, High-Dose Leucovorin and 5-Fluorouracil 48-Hour Continuous Infusion in Pretreated Metastatic Colorectal Cancer: a Phase II Study. Ann. Oncol. 2002;13:1197–1204. DOI: 10.1093/annonc/mdf216.
32. Hegewisch-Becker S., Corovic A., Jaeger E.. Goekkurt J., Panse J., Nierhaus A., Hossfeld D.K., Hossfeld D.K., Pantel K. Whole Body Hyperthermia (WBH, 41.8 °C) Combined with Carboplatin and Etoposide in Advanced Biliary Tract Cancer. Proc. Am. Soc. Clin. Oncol. 2003;22:1247.
33. Douwes F., Bogovi C.J., Douwes O., Migeod F., Grote C. Whole-Body Hyperthermia in Combination with Platinum-Containing Drugs in Patients with Recurrent Ovarian Cancer. Int. J. Clin. Oncol. 2004;9;2:85-91.
34. Richel O.., Zum Vörde Sive Vörding PJ., Rietbroek R., Van der Velden J., Van Dijk J.D., Schilthuis M.S., Westermann A.M. Phase II Study of Carboplatin and Whole Body Hyperthermia (WBH) in Recurrent and Metastatic Cervical Cancer. Gynecol. Oncol. 2004;95;3:680-685.
35. Hildebrandt B., Drager J., Kerner T., Deja M., Löffel J., Stroszczynski C., Ahlers O., Felix R., Riess H., Wust P. Whole-Body Hyperthermia in the Scope of von Ardenne’s ‘Systemic Cancer Multistep Therapy (sCMT)’Combined with Chemotherapy in Patients with Metastatic Colorectal Cancer – a Phase I/II Study. Int. J. Hyperthermia. 2004;20:317–333. DOI: 10.1080/02656730310001637316.
36. Liu X.-L., Fang M.A., Zhou C.-X., Huang M., Gong H.-Y., Xie G.-Y., Hu C.-H. Therapeutic Effect of Whole-Body Hyperthermia Combined with Chemotherapy in Patients with Advanced Cancer. J. Cent South. Univ. (Med Sci). 2006;31;3:350-352.
37. Atmaca A., Al-Batran S.-E., Neumann A., Kolassa Y., Jäger D., Knuth A., Jäger E. Whole-Body Hyperthermia (WBH) in Combination with Carboplatin in Patients with Recurrent Ovarian Cancer – A Phase II Study. Gynecol. Oncol. 2009;112:384–388. DOI:10.1016/j.ygyno.2008.11.001.
38. Bakhshandeh-Bath A., Stoltz A.S., Homann N., Wagner T., Stolting S., Peters S.O. Preclinical and Clinical Aspects of Carboplatin and Gemcitabine Combined with Whole-Body Hyperthermia for Pancreatic Adenocarcinoma. Anticancer Res. 2009;29:3069-3077.
39. Zhao C., Dai C., Chen X. Whole-Body Hyperthermia Combined with Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Stage IV Advanced Gastric Cancer. Int. J. Hyperthermia. 2012;28;8:735-741. DOI:10.3109/02656736.2012.734894.
40. Douwes F.R. Local and Whole Body Hyperthermia in Chemoresistant Ovarian Cancer. Abstracts of the XXXI Conference of the International Clinical Hyperhtermia Society (ICHS). Oncothermia J. 2013;7:70-71.
41. Neumann H., Fabricius H.A., Engelhardt R. Moderate Whole-body Hyperthermia in Combination with Chemotherapy in the Treatment of Small Cell Carcinoma of the Lung: a Pilot Study. Natl. Cancer Inst. Monogr. 1982;61:427-9.42. Engelhardt R. Rationale for Clinical Application of Hyperthermia and Drugs. Strahlentherapie und Oncologie. 1987;163:428-9.
43. Engelhardt R., Muller U., Weth-Simon R., Neumann H.A., Lohr G.W. Treatment of Disseminated Malignant Melanoma with Cisplatin in Combination with Whole-Body Hyperthermia and Doxorubicin. Int. J. Hyperthermia. 1990;6;3:511-515.
44. Zhavrid E.A, Sachivko N.V, Fradkin S.Z, Rudko A.S. Total Hyperthermia in Chemoradiotherapy of Lung Cancer. Voprosy onkologii = Problems in Oncology.1991;37;9-10:962-967 (Russian). [Жаврид Э.А., Сачивко Н.В., Фрадкин С.З., Рудько А.С. Общая гипертермия при химиолучевой терапии рака легкого // Вопросы онкологии. 1991. Т.37, № 9-10. С. 962-967].
45. Rodina A.A. Obshchaya Vysokotemperaturnaya Gipertermiya v Lechenii Nekotorykh Disseminirovannykh Khimiorezistentnykh Opukholey = Total High-Temperature Hyperthermia in the Treatment of Certain Disseminated Chemoresistant Tumors. Extended Abstract of Candidate`s Thesis in Medicine. Nizhniy Novgorod Publ., 2003. 27 p. (In Russian). [Родина А.А. Общая высокотемпературная гипертермия в лечении некоторых диссеминированных химиорезистентных опухолей: Автореф. дис. … канд. мед. наук. Нижний Новгород. 2003. 27 с.].
46. Tikhonova O.A. Obshchaya Gipertermiya v Kompleksnom Lechenii Khimioradiorezistentnykh form Disseminirovannykh Opukholey Osnovnykh Lokalizatsiy = Total Hyperthermia in the Complex Treatment of Chioradio-Resistant Forms of Disseminated Tumors of the Main Localizations. Extended Abstract of Candidate`s Thesis in Medicine. Nizhniy Novgorod Publ., 2002. 22 p.
(In Russian). [Тихонова О.А. Общая гипертермия в комплексном лечении химиорадиорезистентных форм диссеминированных опухолей основных локализаций. Автореф. дис. канд. мед. наук. Нижний Новгород, 2002. 22 с.].
47. Kurpeshev O.K. Obshchaya Gipertermiya pri Disseminirovannykh i Khimiorezistentnykh Formakh Zlokachestvennykh Opukholey = Total Hyperthermia in Disseminated and Chemoresistant Forms of Malignant Tumors. Materialy II Kongressa Onkologov Uzbekistana = Materials of the II Congress of Oncologists of Uzbekistan. Tashkent Publ., 2011.
P. 261-262. (Russian). [Курпешев O.K. Общая гипертермия при диссеминированных и химиорезистентных формах злокачественных опухолей // Материалы II Конгресса онкологов Узбекистана. Ташкент, 2011. С. 261-262].
48. Levin R.D., Sanchez R., Kim Y.D., Mellijor A., Doyle M.A., Simonich W., Williams R.M. Whole Body Hyperthermia Experience in Breast Cancer at American International Hospital. Consensus on Hyperthermia for the 1990s (Edited by
H.I. Bicher et al.). New York, Plenum Press, 1990. P. 387-388.
49. Jaeger D., Atmaca A., Neumann A., Unckell J., Orth J., Jaeger E., Knuth A. 41,8 °C Whole Body Hyperthermia (WBH) Combined with Carboplatin in Patients with Advanced Ovarian Carcinoma. Annals Oncology. 2000;11;4:82.
50. Rethfeldt E., Becker M., Koldovsky P. Whole-Body Hyperthermia in the Treatment of Breast Cancer. 23rd Congress of the International Association for Breast Cancer Research. Abstract. Breast Cancer Research. 2001;3;1:A51. https://doi.org/10.1186/bcr379.
51. Zwischenberger J.B., Vertrees R.A., Bedell E.A. Percutaneous Venovenous Perfusion-Induced Systemic Hyperthermia for Lung Cancer: A Phase I Safety Study. Ann. Thorac. Surg. 2004;77;6:1916-1924; discussion 1925.
52. Xi L., Tekin D., Bhargava P., Kukreja R.C. Whole Body Hyperthermia and Preconditioning of the Heart: Basic Concepts, Complexity, and Potential Mechanisms. Int. J. Hyperthermia. 2001;17;5:439-455.
53. Robins H.I., Kalin N., Shelton S.E., Martin P.A., Shecterle L.M., Barksdale C.M., Neville A.J., Marshall J. Rise in Plasma Beta-Endorphin, ACTH, and Cortisol in Cancer Patients Undergoing Whole Body Hyperthermia. Horm. Metab. Res. 1987;19:441–443. DOI: 10.1055/s-2007-1011847.
54. Hanuscha K.-U., Janssenb C.W. The Impact of Whole-Body Hyperthermia Interventions on Mood and Depression – Are We Ready for Recommendations for Clinical Application? Int.
J. Hyperthermia. 2019;36;1:572–580. https://doi.org/10.1080/02656736.2019.1612103.
55. Locker G.J., Worel N., Bojic A., Heinrich G., Brodowicz T., Bojic A., Heinrich G., Brodowicz T., Clodi M., Funk G.-C., Knöbl P., Zielinski C.C., Köstler W.J. Whole Body Hyperthermia by Extracorporeal Circulation in Spontaneously Breathing Sarcoma Patients: Hemodynamics and Oxygen Metabolism. Int. J. Artif. Organs. 2011;34;11:1085-94. DOI: 10.5301/ijao.5000009. PMID: 22183522.
56. Grosso G., Biondi A., Marventano S., Mistretta A., Calabrese G., Basile F. Major Postoperative Complications and Survival for Colon Cancer Elderly Patients. XXV National Congress of the Italian Society of Geriatric Surgery Padova, Italy. 10-11 May 2012. BMC Surgery. 2012;12;1:S20. http://www.biomedcentral.com/1471-2482/12/S1/S20.
57. Simões C.M., Carmona M.J.C., Hajjar L.A. Vincent J.-L., Landoni G., Belletti A., Vieira J.E., de Almeida J.P., de Almeida E.P., Jr U.R., Kauling A.L., Tutyia C., Tamaoki L., Fukushima J.T., Jr. José O C.A. Predictors of Major Complications after Elective Abdominal Surgery in Cancer Patients. BMC Anesthesiology. 2018;18:49. https://doi.org/10.1186/s12871-018-0516-6.
58. Wehner H., Wey S., Meyer A. Whole Body Hyperthermia Guideline. German Society for Hyperthermia. DGHT
e.V. Version 1.0. October 2018. 2018. 20 p. (German). [Wehner H., Wey S., Meyer A. Whole-Body Hyperthermia Guideline. Deutsche Gesellschaft für Hyperthermie. DGHT e.V. Version 1.0. October 2018. 2018. 20 p.].
59. Кurpeshev OK, Van der Zee J. The Experimental Basis for the Use of Hyperthermia in Oncology. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2018;63;1:57–77. DOI: 10.12737/article_5a8556b4be3e24.36808227. (In Russian). [Курпешев О.К., Ван дер Зее Я. Экспериментальные основы применения гипертермии в онкологии // Медицинская радиология и радиационная безопасность. 2018. Т.63, № 1. С. 57–77. DOI: 10.12737/article_5a8556b4be3e24.36808227].
60. Ito Y., Kobayashi Y., Yatagawa A., Matsuura Y. Effects of Whole-Body Heat Treatment on T Cell-Mediated Immune Response in Cancer Patients. The 6th Asian Congress of Hyperthermic Oncology & The 31st Japanese Congress of Thermal Medicine at Fukui City, Japan. 5-6 September. 2014;171:GSJ35.
61. Takeuchi A., Takeuchi T., Kinjo H., Kotoyori S., Shirahige M., Hasumura H. P53 Gene Therapy Combined with Whole Body Hyperthermia and Local Hyperthermia. The 6th Asian Congress of Hyperthermic Oncology & The 31st Japanese Congress of Thermal Medicine at Fukui City, Japan. 5-6 September. 2014;136:GSE43.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 30.11.2021. Accepted for publication: 30.03.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 3
M.V. Vasin1, L.A. Ilyin2, I.B. Ushakov2
The Phenomenon of Radiation Protection of Large Animals (Dogs) with Indralin
and its Extapolation to Humans
1Russian Medical Academy of Continuous Professional Education, Moscow, Russia
2A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: M.V. Vasin, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
CONTENT
Testing the effectiveness of radioprotectors in large animals is an important stage in the introduction of drugs into the practice of medicine. Unique in scale and world practice, comprehensive studies of the radioprotector of emergency action of the drug B-190 (indralin) in experiments on dogs were carried out. Its high radioprotective efficiency was established with gamma, gamma-neutron and proton high energy irradiation. Under gamma irradiation of dogs indralin at an optimal dose of 30 mg/kg had DRF equel 3, the result of which was not recorded in large animals by any of known radioprotectors. It is important that under non-uniform radiation (shielding of abdomen, head or pelvis), protective effect of indralin doubles. The drug is also active in peroral use. Analysis of extrapolation of experimental data on radioprotective properties of indralin from large animals (dogs) to humans on measurement of succinate dehydrogenase (SDH) activity in lymphocytes of peripheral blood is carried out. Activation of SDH during stress response to acute hypoxia, including under the influence of indralin, is associated with the release of adrenaline and noradrenaline. Catecholamines realize their effect through beta-adrenoceptors on lymphocytes. A close correlation was established between the dose and radioprotective effect of indralin and the growth of SDH lymphocyte activity
(r = 0.99 p < 0.01). Extrapolation of expected radioprotective effect of indralin per person was carried out according to the formula:
DRF = 0.3988e0.009181x[r = 0.995 (0.78–0.9999) p < 0.01], where x is the activity of SDH. DRF of indralin (100 mg intramuscularly) for humans was 1.6. When orally administered indralin at a dose of 450 mg DRF was 1.3.
Keywords: gamma-, gamma-neutron-, proton radiation, indralin, dogs, DRF, SDH, extrapolation
For citation: Vasin MV, Ilyin LA, Ushakov IB. The Phenomenon of Radiation Protection of Large Animals (Dogs) with Indralin and its Extapolation to Humans. Medical Radiology and Radiation Safety. 2022;67(3):5–12. (In Russian). DOI:10.33266/1024-6177-2022-67-3-5-12
References
1. Ilin L.A., Ushakov I.B., Vasin M.V. Radioprotective Drugs in the System of Radiation Protection of Exposed Radiation Workers and Population in the Case of Radiation Accidents // Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2012;57;3:26–31. (In Russian).
2. Ushakov I.B., Vasin M.V. The Drugs and Natural Antioxidants as the Components of Anti-Radiation Countermeasures During Space Flights. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2017;62;4:66-78. (In Russian).
3. Ilin L.A., Rudnyy N.M., Suvorov N.N. Indralin is an Emergency Radioprotector. Protivoluchevyye Svoystva, Farmakologiya, Mekhanizm Deystviya, Klinika = Anti-Radiation Properties, Pharmacology, Mechanism of Action, Clinic. Moscow, Minzdrav RF Publ., 1994. 435 p. (In Russian).
4. Crouch B.G., Overman R.R. Chemical Protection Against X-Irradiation Death in Primates: a Preliminary Report. Science. 1957;125:1092–1093.
5. Jacobus D.P. Protection of the Dog Against Ionizing Radiation. Fed. Proc. 1959;18:74.
6. Jacobus D.P., Dacquisto M.D. Anti-Radiation Drug Development. Military Med. 1961;126:698.
7. Razorenova V.A. Protective Action of Mercamine in Experimental Acute Radiation Injury. Voprosy Patogeneza, Eksperimentalnoy Terapii i Profilaktiki Luchevoy Bolezni = Issues of Pathogenesis, Experimental Therapy and Prevention of Radiation Sickness. Moscow, Medgiz Publ., 1960. P. 351–359. (In Russian).
8. Razorenova V.A., Shcherbova Ye.N. On the Prophylactic Use of Cysteinamine and Cystamine in Acute Radiation Sickness. Meditsinskaya Radiologiya = Medical Radiology. 1961;6;3:266–269. (In Russian).
9. Benson R.E., Michaelson S.M., Downs W. Toxicological and Radioprotection Studies on S-Beta-Aminoethyl Isothiouronium Bromide (AET). Radiat. Res. 1961;15;5:561–567.
10. Mozzhukhin A.S., Rachinskiy F.Yu. Khimicheskaya Profilaktika Radiatsionnykh Porazheniy = Chemical Prophylaxis of Radiation Injuries. Moscow, Atomizdat Publ., 1964. 244 p. (In Russian).
11. Semenov L.F. Profilaktika Ostroy Luchevoy Bolezni = Prevention of Acute Radiation Sickness. Leningrad, Meditsina, 1967. 215 p. (In Russian).
12. Zherebchenko P.G. Protivoluchevyye Svoystva Indolilalkilaminov = Antiradiation Properties of Indolylalkylamines. Moscow, Atomizdat Publ., 1971. 200 p. (In Russian).
13. Chernov G.A., Trushina M.N., Suvorov N.N. Radioprotective Efficacy of Oral Mexamine in Dogs Radiobiologiya. 1973;13;3:464-468. (In Russian).
14. Trushina M.N., Znamenskiy V.V., Chernov G.A., Lemberg V.K. Radioprotective Effect of Oral Mexamine in Monkeys. Radiobiologiya. 1973;13;5:719-722. (In Russian).
15. Semenov L.F., Lapin B.A., Strelkov R.B., et al. Comparative Study of the Anti-Radiation Efficacy of Mexamine and Gaseous Hypoxic Mixture in Experiments on Rhesus Monkeys. Vestnik AMN SSSR. 1978;8:83–88.
(In Russian).
16. Akerfeldt S., Ronnback C., Nelson A. Radioprotective Agents: Results with S-(3-amino-2-Hydroxypropyl) Phosphorothioate, Amidophosphorothioate and Owe Related Compounds. Radiat. Res. 1967;31;4:850–855.
17. Piper J., Stringfellow C., Elliot R., Johnston T. S-2(Omegaa-
minoalkylamino)-Ethyldihydrogen Phosphorothioates and Related Compounds as Potential Antiradiation Agents. J. Med. Chem. 1969;12;2:236–243.
18. Piper J.R., Rose L.M., Johnson T.P. et al. S-2-Omega-Diaminoalkyl Dihydrogen Phosphorothioates as Antiradiation Agents. J. Med. Chem. 1979;22;6:613–639.
19. Yuhas J.M., Storer J.B. Chemoprotection Against Threemodes of Radiation Death in the Mice. Int. J. Radiat. Biol. 1969;15;3:233–237.
20. Yuhas J.M. Biological Factors Affecting the Radioprotective Efficiency of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR-2721) LD50/30 Doses. Radiat. Res. 1970;44;3:621–628.
21. Yuhas J.M. Biological Factors Affecting the Radioprotective Efficiency of S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR-2721) LD50/7 Doses. Radiat. Res. 1971;47;2:226–229.
22. Yuhas J.M., Proctor J.O., Smith L.H. Some Pharmacologic Effects of WR-2721: Their Role in Toxicity and Radioprotection. Radiat. Res. 1973;54;2:222–233.
23. Lu Z. Optimization of Amifostine Administration for Radioprotection. Doctor’s thesis (Ph.). University of Michigan, 2007, 143 p.
24. Wagner M., Sedlmeier H., Metzger E. et al. Untersuchungen zu Toxizität und Strahlenschutz Effect der Chemischen Strahlenschutzsubstanz WR-2721 bei Beagle-Hunden. Teil II: Strahlenschutzeffekt des WR-2721. Strahlentherapie 1980;156:655–662.
25. Stork E.J., Melville G.S.J., Gass A.E. S-2-(3-Aminopropylamino) Ethylphosphorothioic Acid Hydrate as a Radioprotectant in Rodents and Primates. SAM-TR-68-120. Tech Rep SAM, 1968.
26. Vasin M.V., Chernov G.A., Antipov V.V. The Breadth of the Radioprotective Action of Indralin in Comparative Studies on Various Animal Species. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 1997;37;6:896–904. (In Russian).
27. Vasin M.V., Ushakov I.B. Comparative Efficiency and the Window of Radioprotection for Adrenergic and Serotoninergic Agents and Aminothiols in Experiments with Small and Large Animals. J. Radiat. Res. 2015;56;1:1–10. https://doi.org/10.1093/jrr/rru087
28. Vasin M.V. Protivoluchevyye Lekarstvennyye Sredstva = Anti-Radiation Medicines. Moscow, Kniga-Memuar Publ., 2020. 239 p. (In Russian).
29. Vasin M.V. Comparative Characteristics of Modification of Radiosensitivity of Mice and rats by Hypoxic Hypoxia. Radiobiologiya. 1986;26;4:563–565. (In Russian).
30. Antipov V.V., Vasin M.V., Gaydamakin A.N. Specific Features of the Response of SDH Lymphocytes in Animals to Acute Hypoxic Hypoxia and Its Relationship with Radioresistance of the Organism. Kosmicheskaya Biologiya i Aviakosmicheskaya Meditsina = Space Biology and Aerospace Medicine. 1989;23;2:63-66. (In Russian).
31. Ovakimov V.G., Yarmonenko S.P. Modification of the Anti-Radiation Effect of Hypoxic Hypoxia During Artificial Hibernation of the Body. Radiobiologiya. 1975;15;1:69–73. (In Russian).
32. Norris W.P., Fritz T.E., Rehfeld C.E., Poole G.M. Response of Beagle Dog to Cobalt-60 Gamma-radiation. Determination of the LD50 and Description of Associated Changes. Radiat. Res. 1968;35:681-708.
33. MacVittie T.J., Monroy R., Vigmeulle R.M. et al. The Relative Biological Effectiveness of Fission-Neutron-Gamma Radiation on Hematopoietic Syndrome in the Canine: Effect of Therapy on Survival. Radiat. Res. 1991;128;1:S29-S36.
34. MacVittie T.J., Jackson W. Acute Radiation-Induced GI-ARS and H-ARS in a Canine Model of Mixed Neutron/Gamma Relative to Reference Co-60 Gamma Radiation: A Retrospective Study. Health Phys. 2020;119;3;351-357. doi: 10.1097/HP.0000000000001215.
35. Vasin M.V. Poisk i Issledovaniye Novykh Effektivnykh Sredstv Farmakokhimicheskoĭ Zashchity Organizma ot Porazhayushchego Deĭstviya Ioniziruyushchego Izlucheniya v Ryadu Indolilalkilaminov = Search and Study of New Effective Means of Pharmacochemical Protection of the Body from the Damaging Effects of Ionizing Radiation in the Series of Indolylalkylamines, Doctor’s Thesis in Medicine. Moscow, GNIII AiKM MO Publ., 1977. 510 p. (In Russian).
36. Shashkov V.S., Yefimov V.I., Vasin M.V., et al. Indralin - a Novel Effective Radioprotector During Irradiation by High-Energy Protons. Aviakosmicheskaya i Ekologicheskaya Meditsina = Aerospace and Environmental Medicine. 2010;44;1:15-20 (In Russian).
37. Vasin M.V., Ushakov I.B., Koroleva L V. Antipov V.V. The Role of Cellular Hypoxia in the Anti-Radiation Effect of Radioprotectors. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 1999;39;2-3:238-248 (In Russian).
38. Vasin M.V., Ushakov I.B. Activation of Respiratory Chain Complex II as a Hypoxia Tolerance Indicator During Acute Hypoxia. Biofizika = Biophysics. 2018;63;2:329–333 (In Russian).
39. Vasin M.V. B-190 (Indralin) in the Light of History of Formation of Ideasof the Mechanism of Action of Radioprotectors. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2020;60;4:378–395. (In Russian).
40. Nartsissov R.P. Application of p-Nitrotetrazolium Violet for Quantitative Cytochemistry of Human Lymphocyte Dehydrogenases. Arkhiv Anatomii, Gistologii i Embriologii. 1969;56;5:85-92. (In Russian).
41. Koroleva L.V. Radiochuvstvitelnost Organizma i Protivoluchevaya Effektivnost Radioprotektorov v Usloviyakh Sochetannogo Vozdeystviya Ioniziruyushchego Izlucheniya i Normobaricheskoy Giperoksii = Radiosensitivity of The Body and Anti-Radiation Efficiency of Radioprotectors under Conditions of Combined Exposure to Ionizing Radiation and Normobaric Hyperoxia. Diss. Candidate’s Thesis in Medicine. Moscow Publ., 1990. 134 p. (In Russian).
42. Kondrashova M., Zakharchenko M., Khunderyakova N. Preservation of the in Vivo State of Mitochondrial Network for ex Vivo Physiological Study of Mitochondria. Int. J. Biochem. Cell Biol. 2009;41;10:2036-2050. doi: 10.1016/j.biocel.2009.04.020.
43. Kondrashova M.N., Mayevskiy Ye.I., Babayan G.V., et al. Adaptation to Hypoxia by Switching Metabolism to the Transformation of Succinic Acid. Mitokhondrii. Biokhimiya i Ultrastruktura = Mitochondria. Biochemistry and Ultrastructure. Pushchino, Nauka Publ., 1973. P. 112-129 (In Russian).
44. Dhingra R., Kirshenbaum L.A. Succinate Dehydrogenase/Complex II Activity Obligatorily Links Mitochondrial Reserve Respiratory Capacity to Cell Survival in Cardiac Myocytes. Cell. Death Dis. 2015;6;10:e1956. doi: 10.1038/cddis.2015.310.
45. Rustin P., Munnich A., Rötig A. Succinate Dehydrogenase and Human Diseases: New Insights into a Well-Known Enzyme. Europ. J. Hum. Genet. 2002;10;5:289–291. doi: 10.1038/sj.ejhg.5200793.
46. Kondrashova M., Zakharchenko M., Zakharchenko A., et al. Study of Succinate Dehydrogenase and α-Ketoglutarate Dehydrogenase in Mitochondria Inside Glass-Adhered Lymphocytes under Physiological Conditions – the Two Dehydrogenases as Counterparts of Adrenaline and Acetylcholine Regulation. Dehydrogenases. Ed. Canuto R.A. InTech, 2012. P. 235-264. doi: 10.5772/50059. https://www.intechopen.com/chapters/40939.
47. Vetrenko L.M. The Effect of Some Neurotransmitters on the Activity of Succinate Dehydrogenase. Biokhimiya = Biochemistry. 1973;38;1:22-27 (In Russian).
48. Sivaramakrishnan S., Panini S.R., Ramasarma T. Indian J. Biochem. Biophys. 1983;20;1:23-28.
49. Sivaramakrishnan S., Ramasarma T. Noradrenaline Stimulates Succinate Dehydrogenase Through Beta-Adrenergic Receptors. Indian J. Biochem. Biophys. 1983;20;1:16-22.
50. Sanders V.M. The Beta2-Adrenergic Receptor on T and B Lymphocytes: Do We Understand it yet? Brain Behav. Immun. 2012;26;2:195-200. doi: 10.1016/j.bbi.2011.08.001.
51. Vasin M.V., Petrova T.V., Koroleva L.V. Effect of Adrenaline on Cyclic Nucleotides and Succinate Dehydrogenase Activity. Fiziolog. Zhurnal SSSR im. I.M. Sechenova. 1991;77;4:106-108 (In Russian).
52. Vasin M.V., Ushakov I.B., Koroleva L.V., et al. Reaction of the Succinate Oxidase System of Mitochondria of Human Blood Lymphocytes to Adrenaline in Vitro in Healthy People and Patients with Neurovascular Dystonia. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2002. Т.134, № 4. С. 393-396. (In Russian).
53. Vasin M.V., Ushakov I.B. Activation of Respiratory Chain Complex II as a Hypoxia Tolerance Indicator During Acute Hypoxia. Biofizika = Biophysics. 2018;63;2:329–333 (In Russian).
54. Hernansanz-Agustín P., Enríquez J.A. Generation of Reactive Oxygen Species by Mitochondria. Antioxidants. 2021;10;3:415. doi: 10.3390/antiox10030415.
55. Holzer P. Acid-Sensitive Ion Channels and Receptors. Handb. Exp. Pharmacol. 2009;194:283-332. doi: 10.1007/978-3-540-79090-7_9.
56. Picard M., McEwen B.S., Epel E.S., Sandi C. An Energetic View of Stress: Focus on Mitochondria. Front. Neuroendocrinol. 2018;49:72–85. doi: 10.1016/j.yfrne.2018.01.001.
57. Sharma D., Farrar J.D. Adrenergic Regulation of Immune Cell Function and Inflammation. Seminars Immunopathol. 2020;42:709–717.
58. Vasin M.V., Chernov G.A., Koroleva L.V., et al. On the Mechanism of Anti-Radiation Action of Indralin. Radiatsionnaya biologiya. Radioekologiya = Radiation biology. Radioecology. 1996;36;1:36-46 (In Russian).
59. Vasin M.V., Ushakov I.B., Semenova L.A., Kovtun V.Yu. On the Pharmacological Analysis of the Antiradiation Action of Indralin. Radiatsionnaya biologiya. Radioekologiya = Radiation biology. Radioecology. 2001;41;3:307–309 (In Russian).
60. Vasin M.V., Ganshina T.S., Mirzoyan R.S., et al. Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2018;165;3:340-343 (In Russian).
61. Lee Y.-J., Kim H.S., Seo H.S., et al. Stimulation of Alpha1-Adrenergic Receptor Ameliorates Cellular Functions of Multiorgans Beyond Vasomotion Through PPARδ. PPAR Res. 2020;2020:3785137. doi:10.1155/2020/3785137.
62. O’Connell T.D., Jensen B.C., Baker A.J., Simpson P.C. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance. Pharmacol. Rev. 2013;66;1:308-333. doi: 10.1124/pr.112.007203.
63. Vasin M.V., Ushakov I.B., Antipov V.V. Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors. Byulleten Eksperimentalnoy Biologii i Meditsiny = Bulletin of Experimental Biology and Medicine. 2015;159;5:549–552 (In Russian).
64. Ricci A., Bronzetti E., Conterno A. et al. α1-Adrenergic Receptor Subtypes in Human Peripheral Blood Lymphocytes. Hypertension. 1999;33;2:708–712.
65. Bao J.-Y., Huang Y., Wang F. et al. Expression of α-AR subtypes in T-lymphocytes and role of the α-ARs in mediating modulation of T-cell function. Neuroimmunomodul. 2007;14:344–353.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 17.01.2022. Accepted for publication: 15.03.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 3
Yu.S. Belskikh, N.K. Shandala, A.V. Titov, D.V. Isaev, М.P. Semenova,
V.А. Seregin, T.A. Doroneva, Yu.V. Gushchina, A.A. Filonova
Current Radiation Situation at the Remedied Dumps of Mine No. 2
of the Lermontov Production Association Almaz
A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: Yu.S. Belskikh, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Assessment of the current radiation situation around dumps of mine No. 2 of the Lermontov Production Association Almaz after remediation.
Material and methods: The methods of pedestrian gamma survey using the portable spectrometric complex MKS-01A “Multirad-M”.
Soil sampling was used to measure radionuclide specific activities. Activities of gamma emitting radionuclides were measured by a stationary gamma spectrometer of the CANBERRA Company. Activities of 210Po and 210Pb following radiochemical separation of these radionuclides were measured using the radiometric installation UMF-2000.
Short-term measurements of radon EEC were carried out with aerosol alpha-radiometer RAA-20P2 Poisk.
Results: After remediation, gamma ambient dose equivalent rate does not exceed 0,5 μSv/h at all dumps, with the exception of local areas around tunnels No. 9, 10 and 11.
In the area around tunnel No. 9, gamma ambient dose equivalent rate reaches 0,55 μSv/h, in the area of tunnel No. 10–5 μSv/h and higher, and in the area of tunnel No. 11 – up to 0,9 μSv/h.
In the areas around all tunnels, except for tunnel No.11, soil does not belong to solid radioactive waste. In a small area near tunnel No. 11, the content of radionuclides in the soil exceeds the criteria for classifying as solid radioactive waste.
Radon EEC in the surveyed area generally did not exceed 30 Bq/m3. Increased values up to 200 Bq/m3 were registered in the area of tunnel dumps, the mouths of which were not fully isolated (tunnels No. 6, 7 and 10). Moreover, directly at the mouth of tunnel No. 10, radon EEC values reached 65000±11000 Bq/m3.
Conclusions: At all surveyed remedied dumps, except for dumps of tunnels No. 10 and 11, the radiation situation in some areas does not meet the requirements established in the remediation project in accordance with the “Health Care Rules for the Closure, Conservation and Conversion of Enterprises for the Mining and Milling Radioactive Ores” and stay in these territories does not pose a hazard to the population.
Keywords: gamma radiation, natural radionuclides, dumps, uranium mining and milling facility, radiation survey, remediation
For citation: Belskikh YuS, Shandala NK, Titov AV, Isaev DV, Semenova МP, Seregin VА, Doroneva TA, Gushchina YuV, Filono-
va AA. Current Radiation Situation at the Remedied Dumps of Mine No. 2 of the Lermontov Production Association Almaz. Medical Radiology and Radiation Safety. 2022;67(3):21–25. (In Russian). DOI:10.33266/1024-6177-2022-67-3-21-25
References
1. Nesterov Yu.V., Petrukhin N.P. Creation and Development of the Mineral Resource Base of the Russian Nuclear Industry. Moscow Publ., 2017 (In Russ.).
2. Boitsov A.V., Komarov A.V., Nikolsky A.L. Environmental Impact of Uranium Mining and Milling in the Russian Federation 165-175 // Developments in Uranium Resources, Production, Demand and the Environment: Proceedings of a Technical Committee Meeting. Vienna, 15-18 June, 1999. IAEA, Vienna, 2004. IAEA-TECDOC-1425.
3. Yevstratov Ye.V., Agapov A.M., Laverov N.P., Bolshov L.A., Linge I.I. Problemy Yadernogo Naslediya i Puti ikh Resheniya = Nuclear Legacy Problems and Ways to Solve Them. V.1. Moscow, Energopromanalitika Publ., 2012. 356 p. (In Russ.).
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 17.01.2022. Accepted for publication: 15.03.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 3
M.I. Grachev, Yu.A. Salenko, A.V. Simakov,
G.P. Frolov, V.N. Klochkov, Yu.V. Abramov, I.K. Tesnov
Health Effects in Case of Radiation Accidents When Managing Spent Nuclear Fuel
A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: Yu.A. Salenko, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: To consider the features of potential health effects for personnel and for the population in the event of radiation accidents at facilities for post-reactor spent nuclear fuel management (including spent nuclear fuel pools and general plant storage facilities, transportation of nuclear materials and their subsequent processing at radiochemical plants).
Results: Based on the analysis of publications, the potential radiation consequences for personnel and for the population in the event of various types of radiation accidents at the stages of spent nuclear fuel management were systematized.
Conclusion: Advanced technologies underlying the closed nuclear fuel cycle provide a high level of radiation safety for personnel and for the population. At the same time, a large amount of accumulated radioactive and nuclear materials makes it necessary to maintain the health care system in preparedness at all stages of spent nuclear fuel management. Health effects for personnel may be associated with exposure because of criticality accident and internal intake of fission products of uranium and actinides (by inhalation and through wound surfaces).
In case of accidents at radiochemical production, combined radiation-thermal and radiation-chemical injuries are also possible. The main potential hazard for the population in the event of radiation accident at the spent nuclear fuel storage facility is the contamination of the environment and exposure to long-lived uranium fission products and actinides. This requires clarification and development of appropriate criteria and derived intervention levels for making decisions on protective measures.
Hypothetically, the health effects in case of radiation accident when managing “fresh” spent nuclear fuel can be comparable to a large-scale reactor accident and require urgent protective measures, including evacuation and iodine prophylaxis. An important factor that should also be taken into account when planning health care measures is the need for decontamination of victims.
Keywords: spent nuclear fuel, radiation accident, health effects
For citation: Grachev MI, Salenko YuA, Simakov AV, Frolov GP, Klochkov VN, Abramov YuV, Tesnov IK. Health Effects in Case of Radiation Accidents When Managing Spent Nuclear Fuel. Medical Radiology and Radiation Safety. 2022;67(3):13–20.
(In Russian). DOI:10.33266/1024-6177-2022-67-3-13-20
References
1. On Compliance with the Obligations of the Joint Convention on the Safety of Spent Fuel Management and the Safety of Radioactive Waste Management. The Fifth National Report of the Russian Federation. Moscow Publ., 2017. 161 p. (In Russian).
2. Kuryndin A.V., Kirkin A.M., Makovskiy S.V., Gusakov-Stanyukovich I.V. Development of Legal and Regulatory Basis for Approaches to Return of Reprocessing Products of Spent Nuclear Fuel to the Supplier’s State. Yadernaya i Radiatsionnaya Bezopasnost = Nuclear and Radiation Safety Journal. 2020;95;1:15−20. (In Russian).
3. Rachkov V.I., Adamov Ye.O. Scientific and Technical Problems of the Closed Nuclear Fuel Cycle of Two-component Nuclear Power and their Solution in the Project “Proryv”. Zamykaniye Toplivnogo Tsikla Yadernoy Energetiki na Baze Reaktorov na Bystrykh Neytronakh = Closing the Fuel Cycle of Nuclear Power Based on Fast Breeder Reactors. Proceedings of the Conference. Tomsk, 11-12 October, 2018. Moscow Publ., 2020. P. 6−15 (In Russian).
4. Aleksakhin R.M., Buldakov L.A., Gubanov V.A., Drozhko Ye.G., Ilin L.A., Kryshev I.I., et al. Major Radiation Accidents: Consequences and Protective Measures. Ed. Ilin L.A., Gubanov V.A. Moscow, IzdAT Publ., 2001. 752 p. (In Russian).
5. McLaughlin T.P., Monahan Sh.P., Pruvost N.L., Frolov V.V., Ryazanov B.G., Sviridov V.I. A Review of Criticality Accidents. Los Alamos National Laboratory, LA-13638. May 2000. New Mexico, Los Alamos, 2003. 210 p.
6. IAEA. Lessons Learned from the Response to Radiation Emergencies (1945-2010). EPR-Lessons Learned. Vienna, IAEA, 2012. 154 p.
7. Solovyev V.Yu., Ilin L.A., Baranov A.Ye. Radiation Incidents Associated with Human Exposure in the Former USSR Before and after Chernobyl. Desyatiletiye posle CHernobylya: otsenka posledstviy avarii = A Decade after Chernobyl: an Assessment of the Consequences of the Accident. Proceedings of the International Conference. IAEA-CN-63/6. Vienna, 8-12 April, 1997. Vienna, IAEA, 1997. P. 601-607.
8. Solovyev V.Yu., Barabanova A.V., Bushmanov A.Yu., Guskova A.K., Ilin L.A. Review of the Medical Consequences of Radiation Accidents in the Former USSR Territory (Burnasyan FMBC of FMBA of Russia Register Data). Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2013;58;1:36-42 (In Russian).
9. The Fukushima Daiichi Accident. Report by the Director General. GC (59)/14. Vienna, IAEA, 2015. 208 p.
10. Report on the Preliminary Fact Finding Mission Following the Accident at the Nuclear Fuel Processing Facility in Tokaimura, Japan. Vienna, IAEA, 1999. 35 p.
11. IAEA. Method for Developing Arrangements for Response to a Nuclear or Radiological Emergency. EPR-METHOD 2003. Updating IAEA-TECDOC-953. Vienna, IAEA, 2003. 269 p.
12. Recommendation of the International Commission on Radiological Protection. ICRP Publication 103. ICRP. 2007. V.37, No. 2-4. 339 p.
13. Recommendation of the International Commission on Radiological Protection. Radiological Protection of People and the Environment in the Event of a Large Nuclear Accident. ICRP Publication 146. ICRP. 2020. V.49, No.4. 142 p.
14. IAEA. Inventory of Accidents and Losses at Sea Involving Radioactive Material. IAEA-TECDOC-1242. Vienna, IAEA, 2001. 69 p.
15. Barinkov O.P., Kanashov B.A., Komarov S.V., Buchelnikov A.Ye., Shapovalov V.I., Morenko A.I. Preparation of the First Air Transportation of Spent Nuclear Fuel, Certified According to the New Rules. Bezopasnost yadernykh tekhnologiy i okruzhayushchey sredy = Nuclear and Environmental Safety. 2011;1:67-71.
(In Russian).
16. Safety Rules for the Transportation of Radioactive Materials. Federal Rules and Regulations. NP-053-16. 2016 (In Russian).
17. IAEA Safety Standards. Regulations for the Safe Transport of Radioactive Material. 2018 Edition. Specific Safety Requirements No. SSR-6 (Rev.1). Vienna, IAEA, 2018. 165p.
18. Medical Aspects of Countering Radiological and Nuclear Terrorism. Ed. Ilyin L.A. Мoscow, FMBC Im. A.I. Burnasyan Publ., 2018. 392 p. (In Russian).
19. Requirements for planning and ensuring preparedness for the mitigation of the consequences of accidents during the transportation of nuclear materials and radioactive substances. Federal norms and rules. NP-074-06. (In Russian).
20. Zemlyanukhin V.I., Ilyenko Ye.I., Kondratyev A.N., et al. Radiochemical Reprocessing of Nuclear Fuel at Nuclear Power Plants. Moscow: Energoatomizdat Publ., 1989. 280 p. (In Russian).
21. IAEA. The Radiological Accident in the Reprocessing Plant at Tomsk. Vienna: IAEA. 1998. 85 p.
22. Barabanova A.V., Bushmanov A.Yu., Solovyev V.Yu. An Analysis of the Most Severe Cases of Human Irradiation During Radiation Accidents Related to Spontaneous Chain Reaction. Mediko-Biologicheskiye I Sotsialno-Psikhologicheskiye Problemy Bezopasnosti V Chrezvychaynykh Situatsiyakh = Medicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations. 2011;2:32−38. (In Russian).
23. Barabanova A., Wiley A., Bushmanov A. Dose-dependent Analysis of Acute Medical Effects of Mixed Neutron-gamma Radiation from Selected Severe 235U or 239Pu Criticality Accidents in USSR, United States, and Argentina. Health Physics. 2012;102;4:391−399. DOI: 10.1097/HP.0b013e31823b4b78.
24. Bogatov S.A., Gavrilov S.L., Danilyan V.A., Kiselev V.P. Assessment of Radioactive Release for Several Hypothetical Navy Ship Accidents. Moscow Publ., 2001. 33 p. (In Russian).
25. Sokolnikov M.E., Vostrotin V.V., Yefimov A.V., Vasilenko Ye.K., Romanov S.A. Estimates of Lifetime Risk of Lung Cancer Death under Different Scenarios of 239Pu Inhalation. Radiatsiya i risk = Radiation and Risk. 2015;24;3:59-69.
(In Russian).
26. Khokhryakov V.F. «Doses – 1999, 2000» Consequent Development of Plutonium Dosimetry for «Mayak» Personnel. Voprosy Radiatsionnoy Bezopasnosti = Journal of Radiation Safety Issues. 2004;1:71-82. (In Russian).
27. Khokhryakov V.F., Kudryavtseva T.I., Shevkunov V.A. The Risk of Plutonium and Americium Entering the Body of Workers of a Radiochemical Plant through Injured Skin. Atomnaya Energiya = Atomic Energy. 1994;77;6:445-448. (In Russian).
28. Molokanov A., Kukhta B., Galushkin B. Calculation of Internal Dose and Possible Limits for Intakes of Radionuclides in Case of Plutonium Wounds. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2020;65;6:27−37. DOI: 10.12737/1024-6177-2020-65-6-27-37. (In Russian).
29. Grachev M.I., Salenko Yu.A., Abramov Yu.V., Frolov G.P., Klochkov V.N., Kukhta B.A. Operational Values of Radioactive Skin Contamination in the Case of Radiological Accident. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2020;65;3:20−26. DOI: 10.12737/1024-6177-2020-65-3-20-26 (In Russian).
30. Frolov G.P., Salenko Yu.A., Grachev M.I., Galstyan I.A., Klochkov V.N. Decontamination of Victims in the Event of a Radiation Accident at the Stages of Provision Medical Care. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2021;66;3:19−28. DOI: 10.12737/1024-6177-2021-66-3-19-28 (In Russian).
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 17.01.2022. Accepted for publication: 15.03.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 3
V.Yu. Soloviev, E.A. Gudkov
Application of Hematological Test Results for Severity Assessment
of Acute Radiation Injury on Early Stages
A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Contact person: V.Yu. Soloviev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Investigation of the predictive value of information on the concentrations of neutrophils and lymphocytes in the peripheral blood of victims of radiation accidents in the first days (2 to 9) after exposure to predict the severity of acute radiation injury.
Material and methods: Data on the post-radiation dynamics of the concentrations of lymphocytes and neutrophils in the peripheral blood of victims of the accident at the Chernobyl nuclear power plant in 1986 from the database on acute radiation injuries to humans
of the A.I. Burnasyan Federal Medical Biophysical Center was used. Correlation analysis was used as a research method.
Results: Due to the fact that in the period from the 2nd to the 9th day after irradiation, the concentration of lymphocytes in the peripheral blood does not change significantly, and the concentration of neutrophils has a persistent tendency to decrease in the dose range of more than 2 Gy, in addition to the widespread lymphocyte test, operative characteristics for dose-response analysis such as average relative rates of decline in neutrophil concentrations (neutrophil test) and the ratio of neutrophil to lymphocyte concentrations (NLR test) in peripheral blood were proposed. The results of the isolated use of the proposed tests are investigated. The analyzed parameters were the average concentration of lymphocytes on days 2–4 after irradiation and the average relative rates of decrease in the concentration of neutrophils and the ratio of the concentrations of neutrophils to lymphocytes (NLR) in the peripheral blood of the victims. Estimates show that the neutrophil test (σ = 1.16 Gy) has the highest accuracy in the dose range up to 8 Gy with the isolated use of tests compared to the lymphocyte test
(σ = 1.42 Gy) and the NLR test (σ = 1.31 Gy). An algorithm for using the so-called combined test, which is a functional superposition of data on the post-radiation dynamics of the concentration of lymphocytes and neutrophils in peripheral blood in the period from 2 to 9 days after irradiation, which gives a higher predictive accuracy of the dose estimate (σ = 0.9 Gy).
Conclusion: The proposed combined test has a higher predictive value in assessing the severity of acute radiation injury compared with the use of isolated lymphocytic, neutrophilic and NLR tests in clinical practice.
Keywords: radiation accident, ionizing radiation, radiation dosimetry, acute radiation syndrome, lymphocytes, neutrophils
For citation: Soloviev VYu, Gudkov EA. Application of Hematological Test Results for Severity Assessment of Acute Radiation Injury on Early Stages. Medical Radiology and Radiation Safety. 2022;67(3):26–29. (In Russian). DOI:10.33266/1024-6177-2022-67-3-26-29
References
1. Radiation Injuries of Man. Radiatsionnaya Meditsina = Radiation Medicine. Ed. Ilin L.A. Moscow, IZDAT Publ., 2001. V.2. 432 p. (In Russian).
2. Soloviev V.Yu., Samoilov A.S., Lebedev A.O., et al. Application of Time to Emesis Data for Primary Triage of Radiation Accident Victims. Mediko-Biologicheskiye i Sotsialno-Psikhologicheskiye Problemy Bezopasnosti v Chrezvychaynykh Situatsiyakh = Medicо-Biological and Socio-Psychological Problems of Safety in Emergency Situations. 2021;1:14-7. DOI: 10.25016/2541-7487-2021-0-1-14-21 (In Russian).
3. Goans R.E., Holloway E.C., Berger M.E., Ricks R.C. Early Dose Assessment in Criticality Accidents. Health Physics. 2001;81;4:446-449. DOI: 10.1097/00004032-200110000-00009.
4. Parker D.D., Parker J.C. Estimating Radiation Dose from Time to Emesis and Lymphocyte Depletion. Health Physics. 2007;93;6:701-704. DOI: 10.1097/01.HP.0000275289.45882.29.
5. Koenig K.L., Goans R.E., Hatchett R.J. et al. Medical Treatment of Radiological Casualties: Current Concepts. Annals of Emergency Medicine. 2005;45;6:643-652. DOI:10.1016/j.annemergmed.2005.01.020.
6. Acute Radiation Syndrome. Atlas. Eds. Samoilov A.S., Soloviev V.Yu. M.: SRC-FMBC, 2019. 232 p.
7. Goans R.E., Iddins C.J. The Neutrophil to Lymphocyte Ratio as a Triage Tool in Criticality Accidents. Health Physics. 2021;120;4:410-416. DOI: 10.1097/HP.0000000000001342.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 17.01.2022. Accepted for publication: 15.03.2022.