JOURNAL DESCRIPTION

The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.

Members of the editorial board are scientists specializing in the field of radiation biology and medicine, radiation protection, radiation epidemiology, radiation oncology, radiation diagnostics and therapy, nuclear medicine and medical physics. The editorial board consists of academicians (members of the Russian Academy of Science (RAS)), the full member of Academy of Medical Sciences of the Republic of Armenia, corresponding members of the RAS, Doctors of Medicine, professor, candidates and doctors of biological, physical mathematics and engineering sciences. The editorial board is constantly replenished by experts who work in the CIS and foreign countries.

Six issues of the journal are published per year, the volume is 13.5 conventional printed sheets, 88 printer’s sheets, 1.000 copies. The journal has an identical full-text electronic version, which, simultaneously with the printed version and color drawings, is posted on the sites of the Scientific Electronic Library (SEL) and the journal's website. The journal is distributed through the Rospechat Agency under the contract № 7407 of June 16, 2006, through individual buyers and commercial structures. The publication of articles is free.

The journal is included in the List of Russian Reviewed Scientific Journals of the Higher Attestation Commission. Since 2008 the journal has been available on the Internet and indexed in the RISC database which is placed on Web of Science. Since February 2nd, 2018, the journal "Medical Radiology and Radiation Safety" has been indexed in the SCOPUS abstract and citation database.

Brief electronic versions of the Journal have been publicly available since 2005 on the website of the Medical Radiology and Radiation Safety Journal: http://www.medradiol.ru. Since 2011, all issues of the journal as a whole are publicly available, and since 2016 - full-text versions of scientific articles. Since 2005, subscribers can purchase full versions of other articles of any issue only through the National Electronic Library. The editor of the Medical Radiology and Radiation Safety Journal in accordance with the National Electronic Library agreement has been providing the Library with all its production since 2005 until now.

The main working language of the journal is Russian, an additional language is English, which is used to write titles of articles, information about authors, annotations, key words, a list of literature.

Since 2017 the journal Medical Radiology and Radiation Safety has switched to digital identification of publications, assigning to each article the identifier of the digital object (DOI), which greatly accelerated the search for the location of the article on the Internet. In future it is planned to publish the English-language version of the journal Medical Radiology and Radiation Safety for its development. In order to obtain information about the publication activity of the journal in March 2015, a counter of readers' references to the materials posted on the site from 2005 to the present which is placed on the journal's website. During 2015 - 2016 years on average there were no more than 100-170 handlings per day. Publication of a number of articles, as well as electronic versions of profile monographs and collections in the public domain, dramatically increased the number of handlings to the journal's website to 500 - 800 per day, and the total number of visits to the site at the end of 2017 was more than 230.000.

The two-year impact factor of RISC, according to data for 2017, was 0.439, taking into account citation from all sources - 0.570, and the five-year impact factor of RISC - 0.352.

Medical Radiology and Radiation Safety. 2015. Vol. 60. No. 1. P. 45-53

REVIEW

V.Y. Kovtun1, V.D. Gladkih1, Y.A. Davidovuch1, E.S. Zhorova2, V.V. Ogorodnikova1, I.K. Belyaev2, V.I. Krasnjuk2

Drug Formulation of the Ca-DTPA and Zn-DTPA

1. Federal State Establishment Science and Engineering Сenter «Pharmzashchita» FMBA of Russia, Khimki, Russia, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; 2. A.I. Burnasyan Federal Medical Biophysical Center of FMBA, Moscow, Russia

ABSTRACT

Purpose: To analyze modern approaches to using of therapeutic forms of DTPA (Ca-DTPA and a Zn-DTPA) for enhance the elimination of transuranium elements and decrease the dose formation of internal exposure.

Materials and methods: The content-analysis of publications related to development, pharmacokinetics and practical using of chelating compounds.

Results: Among the complexons used for prevention and treatment of radionuclide incorporation in the developed countries (the USA, the European community, Japan, China) for medical using allowed Ca-DTPA and Zn-DTPA as inhalations and injection solutions. In Russia Ca-DTPA only is allowed. The comparative characteristic of properties Ca-DTPA and Zn-DTPA testifies to basic uniformity of their biological effect. At the same time Zn-DTPA is characterized by less expressed toxicity and selectivity of action concerning nuclides. Hundreds of patients have been treated with Zn-DTPA; its efficiency, safety and smaller toxicity were shown. In Russia this compound isn’t allowed for medical use. It is necessary to make the maximum efforts for correction of such situation.

Conclusions: Considering features of biological effect of Ca-DTPA and Zn-DTPA the expedient scheme of treatment can be proposed: first Ca-DTPA, second Zn-DTPA. This scheme increases efficiency and reduces negative manifestations of prolonged using of Ca-DTPA in the monotherapy mode.

Key words: chelate, drug formulation, pentacinum, zinkacinum, internally deposited transuranic elements, drug for removing

REFERENCES

  1. Schwarzenbach G., Kampitsch T., Steiner R., Komplexone I. Über die Salzbildung der Nitrilotriessigsäure. Helv. Chim. Acta. 1945. Vol. 28. No. 1. P. 828-840.
  2. Schwarzenbach G., Kampitsch T., Steiner R. Komplexone II. Das Komplexbildungsvermögen von Iminodiessgsäure, Methyliminodiessgsäure, Aminomalonsäure und Aminomalonsäure-diessgsäure. Chim. Acta. 1945. Vol. 28. No. 1. P. 1133-1143.
  3. Semenov D.I., Tregubenko I.P. Kompleksony v biologii i meditsine. Sverdlovsk, UNTs AN SSSR. 1984. 289 p.
  4. Teoreticheskie osnovy i prakticheskoe primenenie. Transl. for German. Moscow, Goskhimizdat. 1958. 246 p.
  5. Semenov D.I. Kompleksony v biologii i meditsine. Priroda. 1959. No. 8. P. 25-32.
  6. Dyatlova N.M., Temkina V.Ya., Kolpakova I.D. Kompleksony. Moscow: Khimiya. 1970. 416 p.
  7. Tikhonova L.I. Kompleksoobrazovanie tsirkoniya s nekotorymi poliaminopoliuksusnymi kislotami. Zh. neorg. khim. 1967. Vol. 12. No. 4. P. 939-943.
  8. Razbitnaya L.M. Issledovaniya kompleksoobrazovaniya tseriya, ittriya i uranila s poliaminopoliuksusnymi kislotami. Avtoreferat dis. kand. khim. nauk. Moscow. 1964. 22 p.
  9. Moskvin A.I. Issledovaniya kompleksoobrazovaniya Pu3+, Am3+, Cm3+ c nitrilotriuksusnoi i dietilentriaminpentauksusnoi kislotami. Radiokhimiya. 1971. Vol. 13. No. 4. P. 575-581.
  10. Piskunov E.M., Rykov A.G. Issledovaniya kompleksoobrazovaniya s DTPA. Torii (IV). Radiokhimiya. 1972. Vol. 14. No. 2. P. 260-264.
  11. Piskunov E.M., Rykov A.G. Issledovaniya kompleksoobrazovaniya s DTPA. Uran (IV). Radiokhimiya. 1972. Vol. 14. No. 2. P. 265-268.
  12. Piskunov E.M., Rykov A.G. Issledovaniya kompleksoobrazovaniya s DTPA. Plutonii (IV). Radiokhimiya. 1972. 14. No. 2. P. 332-334.
  13. Catsch A. Experimenteller Beitrage zur Frage der Bleidelkorporation durch Chelatbildner. Arzneim.-Forsch. 1967. Vol. 17. P. 493-495.
  14. Chiadot P., Lafuma J. Toxicité aiguё des chelatants thérapeutiques utilisables dans l’industrie nucléaire. Rev. d’hygiene Med. Soc. 1962. Vol. 10. P. 391-401.
  15. Planas-Bohne F., Ebel H. Dependence of DTPA-toxicity on the treatment schedule. Health Phys. 1975. Vol. 29. No. 1. P. 103-106.
  16. Health physics in the People’s Republic of China. Health Phys. 1981. Vol. 41. No. 3. P. 585-588.
  17. Volf V. Treatment of incorporated transuranum element. Techn. Rep. Series. No. 184. Vienna: IAEA. 1978, 168 p.
  18. Seidel A. Metabolismus und Toxizität Therapeutischer Chelatbildner. Strahlentherapie. 1970. Vol. 139. No. 7. P. 603-610.
  19. Doolan P.D., Schwartz S.L., Hayes I.R. et al. An evaluation of the nefrotoxicity of ethylenediaminetetraacetate and diethylentriaminetetraacetate in the rat. Appl. Pharmacol. 1967. Vol. 10. No. 3. P. 481-500.
  20. Srot Z., Zylicz E., Zablotna R. et al. Badania porownawcze toksycznosci I effectywnosci chelatow kwasu dwuetylentrojaminopieiooctawego: Na3CaDTPA, Na3ZnDTPA i Na3MnDTPA stosowanych do usuwania 46Sc, 65Zn i 144Ce z organizmu szczura. Nucloonia. 1974. Vol. 19. No. 10. P. 917-931.
  21. Taylor G.N., Williams J.L., Roberts H. et al. Increased toxicity of Na3CaDTPA when given by protracted administration. Health Phys. 1974. Vol. 27. No. 3. P. 285-288.
  22. Ebel H. Metabolismus und Toxizität therapeutischer Chelatbildner. Strahlentherapie. Vol. 149. No. 4. P. 450-456.
  23. Taylor G.N., Mays Ch.W. Fetal injury induced by CaDTPA in dogs. Health Phys. 1978. Vol. 35. No. 6. P. 858-860.
  24. Brummett E.S., Mays Ch.W. Teratological studies of ZnDTPA in mice. Health Phys. 1977. Vol. 33. No. 6. P. 624-626.
  25. Calder S.E., Mays Ch.W., Taylor G.N., Brammer Th. Zn-DTPA safety in the mouse fetus. Health Phys. 1979. Vol. 36. No. 4. P. 524-526.
  26. Mays Ch.W., Taylor G.N., Fischer D.R. Estimated toxicity of Ca-DTPA to the human fetus. Health Phys. 1976. Vol. 30. No. 2. P. 247-249.
  27. Reuters T. Pentetate calcium Trisodium. Micromedex, Poisindex, Management. 2011. 21 p.
  28. Seidel A., Volf V. Removal of internally deposited transuranium elements by Zn-DTPA. Health Phys. 1972. Vol. 22. No. 6. P. 779-783.
  29. Taylor G.N., Lloyd R.D., Boseman J.J. et al. Removal of plutonium from beagles using Ca-DTPA and Zn-DTPA: Effects of initial DTPA injection. Health Phys. 1978. Vol. 35. No. 2. P. 201-210.
  30. Carbaugh E.H., Lynch T.P., Cannon C.N. et al. Case study: three acute 241Am inhalations with DTPA therapy. Health Phys., 2010. Vol. 99. No. 4. P. 539-546.
  31. Akashi M., Tanosaki S., Kuroiwa N. et al. Effects of a chelating agent DTPA on excretion of heavy metal ions in healthy volunteers. In “IRPA 10, 10th Internat. Congress of the internat. Radiation Protection”. P-3a-194. 2000. Hiroshima.
  32. Catsch A. Removal of transuranic elements by chelating agents. Facts, open questions and prospects. In “Diagnosis and Treatment of Incorporated Radionuclides”. Vienna: IAEA. 1976. P. 295-305.
  33. Lineoln T.A. The use of DTPA and induced sputum as diagnostic techniques after internal contamination. In “Diagnosis and Treatment of Incorporated Radionuclides”. IAEA. 1976. P. 203-208.
  34. Gasteva G.N., Krasnyuk V.I., Bad'in V.I. et al. Klinicheskaya otsenka perenosimosti i effektivnosti preparata «tsinkatsin» pri inkorporatsii plutoniya i ameritsiya v organizm cheloveka. Meditsina truda i prom. ekologiya. 2005. No. 3. P. 42-45.
  35. Shchadilov A.E., Khokhryakov V.F., Kudryavtseva T.I. et al. Vliyanie pentatsina na uroven' ekskretsii plutoniya iz organizma cheloveka. Byull. sibir. med. 2005. Vol. 2. P. 128-132.
  36. Grappin L., Berard Ph., Menetrier F. et al. Exposure to actinides: report on Ca-DTPA injections in CEA-AREVA centres. Radioprotection. 2007. Vol. 42. No. 2. P. 163-196.
  37. Ohlenschlager L. Efficacy of Zn-DTPA in removing plutonium from the human body. Health Phys. 1976. Vol. 30. No. 2. P. 249-250.
  38. Ohlenschlager L., Schieferdecker H., Smidt-Martin W. Efficacy of Zn-DTPA and Ca-DTPA in removing plutonium from the human body. Health Phys. 1978. Vol. 35. No. 5. P. 694-699.
  39. Robinson B., Heid K.R., Aldridge T.H., Glenn R.D. 1976 Hanford Americium Exposure Incident: organ burden and radiation dose estimates. Health Phys. 1983. Vol. 45. No. 4. P. 911-921.
  40. Lyubchanskii E.R. Primenenie Na3Ca DTPA (pentatsina) dlya udaleniya Pu239 iz organizma krys pri ingalyatsionnom porazhenii. Medical Radiology and Radiation Safety. 1965. Vol. 10. No. 1. P. 45-49.
  41. Lyubchanskii E.R. Primenenie Na3Ca DTPA (pentatsina) dlya vyvedeniya Pu239 iz organizma krys pri ingalyatsionnom porazhenii. V kn. «Raspredelenie i biologicheskoe deistvie radioaktivnykh izotopov». Moscow: Atomizdat. 1966. P. 471-476.
  42. Lyubchanskii E.R., Koshurnikova N.A. Profilakticheskoe primenenie aerozolei DTPA u krys pri khronicheskoi ingalyatsii Pu239. Med. radiol. 1968. Vol. 13. No. 10. P. 46-51.
  43. Koshurnikova N.A., Lyubchanskii E.R. Vliyanie profilakticheskogo vdykhaniya pentatsina na otdalennye posledstviya ingalyatsii Pu239. Med. radiol. 1969. Vol. 14. No. 9. P. 29-34.
  44. Dudley R.E, Muggenburg B.A., Cuddihy R.G. et al. Nasal absorption of DTPA in rats. Health Phys. 1980. Vol. 38. No. 5. P. 763-768.
  45. Dudley R.E., Muggenburg B.A., Cuddihy R.G. et al. Absorption of DTPA from the respiratory tracts of beagle dogs. LF-60 (12-78). 1978. P. 195-199. (TsNII Atominform No. 517331).
  46. Stather J.W., Smith H., Bailey M.R. et al. The retention of 14C-DTPA in human volunteers after inhalation or intravenous injection. Health Phys. 1983. Vol. 44. No. 1. P. 45-52.
  47. Aronson A.L., Hammond P.B. Effect of two chelating agents on the distribution and excretion of lead. J. Pharm. Ther. 1964. Vol. 146. P. 241-251.
  48. Bohne F., Harmuth-Hoene A.E., KÜrzinger K. et al. Metabolism und Toxizität therapeutischer Chelatbildner XII. Strahlentherapie. 1968. Vol. 136. No. 5. P. 609-616.
  49. Bohne F., Harmuth-Hoene A.E., Weber K.M. Vergleichende Untersuchungen Über die Wirksamkeit von Chelatbildnern bei der Experimentellen Eisenpeicherkrankheit der Ratte. Naunyn-Schmiedebergs Arch. Pharmak. u. exp. Path. 1967. Vol. 257. P. 409-419.
  50. Patent USA № 7914767. Oral DTPA for radionuclide chelation. 2011.
  51. Reddy J.D., Cobb R.R., Dungan N.W. et al. Preclinical toxicology, pharmacology, and efficacy of a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation. Drug Dev. Res. 2012. Vol. 73. No. 5. P. 232-242.
  52. Hanker G.N., Weber W., Doyle-Eisele M. et al. Efficacy of a novel orally administered formulation DTPA tablets for decorporating an intravenously injected radionuclide: a comparison with intravenously administered licensed DTPA. Drug Dev. Res. 2012. Vol. 73. No. 5. P. 290-298.
  53. Patent USA US RE No. 42748 E. Oral DTPA for radionuclide chelation.
  54. Shankar G.N., Weber W., Doyle-Eisele M. et al. Improved decorporation of the actinide radioelement Am-241 with a novel orally available formulation of DTPA - efficacy and pharmacokinetic studies. In: ICRR2011, 14th International Congress of Radiation Research. POS23-65. 2011. Warszawa.
  55. Shankar G.N., Weber W., Doyle-Eisele M. et al. Efficacy of novel orally administered formulation of DTPA tablets for decorporating an intravenously injected radionuclide: a comparison with intravenously administered licensed DTPA. Drug Dev. Res. 2012. Vol. 73. No. 5. P. 290-298.
  56. Shankar G.N., Potharaju S., Green C.N. Evaluating the toxicity of novel Zn-DTPA tablet formulation in dogs and rats. Drug Dev. Res. 2014. Vol. 75. No. 1. P. 37-46.
  57. Pentetate calcium trisodium injection. Instruction for use. Available from: www.fda.gov/downloads/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/USM131638.pdf. 2004.
  58. Pentetate zinc trisodium injection. Instruction for use.Available from: www.fda.gov/downloads/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/USM131639.pdf. 2004.
  59. Calcium DTPA and Zinc DTPA drug products - submitting a new drug application. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research. August 2004. Available from: http://www.fda.gov/cder/guidance/index.htm.
  60. Decorporation of radionuclides from the human body. Eds. Henge-Napoli M.N., Stradling G.N., Taylor D.M. Radiat. Prot. Dosim. Special issue. 2000. Vol. 87. No. 1. EUR Report 19330.
  61. Guidebook for the treatment of accidental internal radionuclide contamination of workers. Gerber G.B., Thomas R.S. Radiat. Prot. Dosim. 1992. Vol. 41. No. 1, 49 p.
  62. Ohlenschlager L. Efficacy of Zn-DTPA in removing plutonium from the human body. Health Phys. 1976. Vol. 30. No. 2. P. 249-250.
  63. Ohlenschlager L., Schieferdecker H., Smidt-Martin W. Efficacy of Zn-DTPA and Ca-DTPA in removing plutonium from the human body Health Phys. 1978. Vol. 35. No. 5. P. 694-699.
  64. Robinson B., Heid K.R., Aldridge T.H., Glenn R.D. 1976 Hanford Americium Exposure Incident: organ burden and radiation dose estimates. Health Phys. 1983. Vol. 45. No. 4. P. 911-921.
  65. Breitenstein B.D., Palmer H.E. Lifetime follow-up of the 1976 americium accident victum. Radiat.Prot.Dosim. 1989. Vol. 26. No. 1-4. P. 317-322.
  66. Girand J.-M. Bilan de l’utilisation du DTPA au CEA et à la COGEMA. Electricite de France - Service de Radioprotection. Document No. 17, March 2001. 5 p.
  67. Homeland security presidentaldirective. HSPD-18. Available from: http://www.fas.org/irp/offdocs/hspd-18.html. 2007.
  68. Homeland security presidentaldirective. HSPD-21. Available from: http://www.fas.org/irp/offdocs/hspd-21.html. 2007.

For citation: Kovtun VY, Gladkih VD, Davidovuch YA, Zhorova ES, Ogorodnikova VV, Belyaev IK, Krasnjuk VI. Drug Formulation of the Ca-DTPA and Zn-DTPA. Medical Radiology and Radiation Safety. 2015;60(1):45-53. Russian.

PDF (RUS) Full-text article (in Russian)

Contact Information

 

46, Zhivopisnaya st., 123098, Moscow, Russia Phone: +7 (499) 190-95-51. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal location

Attendance

2766152
Today
Yesterday
This week
Last week
This month
Last month
For all time
2046
4471
24536
18409
73895
75709
2766152

Forecast today
3024


Your IP:216.73.216.31