Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals
195mPt has been obtained in reaction ¹⁹⁷Au(g,np)¹⁹⁵mPt on the electron linear accelerator with energy 40 MeV and current 10 mA. To produce ¹⁹⁵mPt from a target of gold the extractor such as Kuchera-Shtoly was needed. The following stage of technology consisted in obtaining synthetic cisplatin on a b...
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Національний науковий центр «Харківський фізико-технічний інститут» НАН України
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| Цитувати: | Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals / N.P. Dikiy, A.N. Dovbnya, Y.V. Lyashko, E.P. Medvedeva, D.V. Medvedev, V.L. Uvarov, L.D. Gritsan, N.I. Onishchenko // Вопросы атомной науки и техники. — 2008. — № 5. — С. 198-202. — Бібліогр.: 8 назв. — англ. |
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irk-123456789-1115582017-01-11T03:04:03Z Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals Dikiy, N.P. Dovbnya, A.N. Lyashko, Y.V. Medvedeva, E.P. Medvedev, D.V. Uvarov, V.L. Gritsan, L.D. Onishchenko, N.I. Применение ускорителей 195mPt has been obtained in reaction ¹⁹⁷Au(g,np)¹⁹⁵mPt on the electron linear accelerator with energy 40 MeV and current 10 mA. To produce ¹⁹⁵mPt from a target of gold the extractor such as Kuchera-Shtoly was needed. The following stage of technology consisted in obtaining synthetic cisplatin on a basis ¹⁹⁵mPt. The admixture of activity ¹⁹⁶Au in synthesized cisplatin was 1.4% relatively of the ¹⁹⁵mPt activity. The effective dozes have been measured in various organs of animals after administration of cisplatin containing ¹⁹⁵mPt with activity 13 kBq. It has been shown that effective dozes from ¹⁹⁵mPt cisplatin for various organs were from 0.72 to 0.20 mGy/MBq. Проведено експерименти по виділенню ізотопу платини ¹⁹⁵mPt у реакції ¹⁹⁷Au(g,np)¹⁹⁵mPt на лінійному прискорювачі електронів з енергією 40 МеВ і струмом 10 мкА. Розроблено технологію виділення ¹⁹⁵mPt з мішені золота в екстракторі типу Кучера-Штоля. Одержано синтетичний цисплатин на основі ¹⁹⁵mPt. Домішка ¹⁹⁶Au у синтезованому цисплатину склала 1,4% від активності ¹⁹⁵mPt. Виміряні ефективні дози поглинання на одиницю активності від ¹⁹⁵mPt у різних органах тварин, яким був уведений радіоактивний цисплатин у дозі 13 кБк. Показано, що дози поглинання ¹⁹⁵mPt цисплатина для різних органів становили від 0,72 до 0,20 мГр/MБк. Проведены эксперименты по выделению изотопа платины ¹⁹⁵mPt в реакции ¹⁹⁷Au(g,np)¹⁹⁵mPt на линейном ускорителе электронов для энергии 40 МэВ при токе 10 мкА. Разработана технология выделения ¹⁹⁵mPt из мишени золота в экстракторе типа Кучера-Штоля. Следующий этап технологии заключался в получении синтетического цисплатина на основе ¹⁹⁵mPt. Примесь ¹⁹⁶Au в синтезированном цисплатине составила 1,4% от активности ¹⁹⁵mPt. Измерены эффективные дозы поглощения на единицу активности от ¹⁹⁵mPt в различных органах животных, которым был введен радиоактивный цисплатин в дозе 13 кБк. Показано, что дозы поглощения от ¹⁹⁵mPt для различных органов составляли от 0,72 до 0,20 мГр/MБк. 2008 Article Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals / N.P. Dikiy, A.N. Dovbnya, Y.V. Lyashko, E.P. Medvedeva, D.V. Medvedev, V.L. Uvarov, L.D. Gritsan, N.I. Onishchenko // Вопросы атомной науки и техники. — 2008. — № 5. — С. 198-202. — Бібліогр.: 8 назв. — англ. 1562-6016 PACS: 29.17.+w http://dspace.nbuv.gov.ua/handle/123456789/111558 en Вопросы атомной науки и техники Національний науковий центр «Харківський фізико-технічний інститут» НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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English |
| topic |
Применение ускорителей Применение ускорителей |
| spellingShingle |
Применение ускорителей Применение ускорителей Dikiy, N.P. Dovbnya, A.N. Lyashko, Y.V. Medvedeva, E.P. Medvedev, D.V. Uvarov, V.L. Gritsan, L.D. Onishchenko, N.I. Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals Вопросы атомной науки и техники |
| description |
195mPt has been obtained in reaction ¹⁹⁷Au(g,np)¹⁹⁵mPt on the electron linear accelerator with energy 40 MeV and current 10 mA. To produce ¹⁹⁵mPt from a target of gold the extractor such as Kuchera-Shtoly was needed. The following stage of technology consisted in obtaining synthetic cisplatin on a basis ¹⁹⁵mPt. The admixture of activity ¹⁹⁶Au in synthesized cisplatin was 1.4% relatively of the ¹⁹⁵mPt activity. The effective dozes have been measured in various organs of animals after administration of cisplatin containing ¹⁹⁵mPt with activity 13 kBq. It has been shown that effective dozes from ¹⁹⁵mPt cisplatin for various organs were from 0.72 to 0.20 mGy/MBq. |
| format |
Article |
| author |
Dikiy, N.P. Dovbnya, A.N. Lyashko, Y.V. Medvedeva, E.P. Medvedev, D.V. Uvarov, V.L. Gritsan, L.D. Onishchenko, N.I. |
| author_facet |
Dikiy, N.P. Dovbnya, A.N. Lyashko, Y.V. Medvedeva, E.P. Medvedev, D.V. Uvarov, V.L. Gritsan, L.D. Onishchenko, N.I. |
| author_sort |
Dikiy, N.P. |
| title |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals |
| title_short |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals |
| title_full |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals |
| title_fullStr |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals |
| title_full_unstemmed |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals |
| title_sort |
estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mpt in various organs of animals |
| publisher |
Національний науковий центр «Харківський фізико-технічний інститут» НАН України |
| publishDate |
2008 |
| topic_facet |
Применение ускорителей |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/111558 |
| citation_txt |
Estimation of the absorbed doses of synthesized cisplatin with ¹⁹⁵mPt in various organs of animals / N.P. Dikiy, A.N. Dovbnya, Y.V. Lyashko, E.P. Medvedeva, D.V. Medvedev, V.L. Uvarov, L.D. Gritsan, N.I. Onishchenko // Вопросы атомной науки и техники. — 2008. — № 5. — С. 198-202. — Бібліогр.: 8 назв. — англ. |
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Вопросы атомной науки и техники |
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| fulltext |
ESTIMATION OF THE ABSORBED DOSES OF SYNTHESIZED
CISPLATIN WITH 195mPt IN VARIOUS ORGANS OF ANIMALS
N.P. Dikiy, A.N. Dovbnya, Yu.V. Lyashko, E.P. Medvedeva,
D.V. Medvedev, V.L. Uvarov, L.D. Gritsan, N.I. Onishchenko
National Science Center “Kharkov Institute of Physics and Technology”, Kharkov, Ukraine
E-mail:ndikiy@kipt.kharkov.ua
195mPt has been obtained in reaction 197Au(γ,np)195mPt on the electron linear accelerator with energy 40 MeV and
current 10 µA. To produce 195mPt from a target of gold the extractor such as Kuchera-Shtoly was needed. The fol-
lowing stage of technology consisted in obtaining synthetic cisplatin on a basis 195mPt. The admixture of activity
196Au in synthesized cisplatin was 1.4% relatively of the 195mPt activity. The effective dozes have been measured in
various organs of animals after administration of cisplatin containing 195mPt with activity 13 kBq. It has been shown
that effective dozes from 195mPt cisplatin for various organs were from 0.72 to 0.20 mGy/MBq.
PACS: 29.17.+w
1. INTRODUCTION
In recent years a large series of new antineoplastic
preparations have been developed. The combination of
these drugs with radiotherapy enabled to develop and
update the schemes and regimens of their optimal use,
as well as, to increase the efficiency of cancer-carrier
treatment. In Ukraine the oncologists have in their arse-
nal more than 70 antineoplastic preparations [1-2].
However, despite the achievements in this field some of
these drugs are imperfect and most of them have a low
selective action. Therefore, there is an urgent need to
develop new pharmaceuticals, update the available ones
and to combine the treatment regimens. The main rea-
son for this is a necessity of decreasing the toxic influ-
ence of drugs, reducing the painful symptoms and in-
creasing the patient life.
Among the chemical preparations exerting an antitu-
moral action are the complex compounds of transition
metals, in particular, platinum compounds. For the most
part, antitumor drags are organic matters by the chemi-
cal structure. In this context cisplatin is a premier inor-
ganic and effective antitumor drug. Just the geometrical
configuration of platinum complexes plays an important
role not only in a sense of changing their physical-me-
chanical properties, but, also, their biological activity.
Labeling of cisplatin by the 195mPt isotope makes it
possible to use a high value of Auger electron
bremsstrahlung losses in the cell nucleus. A synergism
influence due to the bystander effect should be noted
too. Production of radioactive cisplatin is possible by ir-
radiating prepared pharmaceuticals. In this case the radi-
ation doses not leading to the cisplatin molecule de-
struction are permissible. In the case of platinum irradi-
ation with high radiation beams a further synthesis of
radioactive cisplatin is necessary.
The advantages of 195mPt use for labeling radiotracers
provoked many attempts of 195mPt synthesis [3]. Howev-
er, the obtained specific activities (30-50 Bq/mg) of ra-
diotracers have not permitted to reach significant results
in the tumor treatment. Successful efforts for production
of 195mPt with a high specific activity were undertaken in
the USA, Oak Ridge. By the double neutron capture in
the reactor, being the most intense in the world, a spe-
cific activity of 195mPt near 80 mCi/mg was reached [4].
2. PROCEDURE OF 195mPt EXTRACTION
The article presents and discusses the conditions of
cisplatin (Mili Healthcare LC, GB) at 26- and – 34 MeV
electron accelerators using the bremsstrahlung. In this
case the radioactive cisplatin makes 1000 Bq/mg of cis-
platin. At a dose of 5 Gr the destruction of cisplatin
molecule occurs that appears in the form of a fine sus-
pension in the preparation. At a dose more than 10 Gr a
brown precipitate settles out from cisplatin preparation.
The use of crystalline cisplatin allows one to in-
crease the irradiation dose. At an irradiation dose of
more than 10 Gr there occurs significant destruction of
the crystalline cisplatin molecule. However, the most
part of crystalline cisplatin conserve their structure. Af-
ter separation of the destroyed cisplatin, the specific ac-
tivity of radioactive crystalline cisplatin was determined
at a level of 2 kBq/mg.
We performed the synthesis of radioactive cisplatin
from irradiated samples of crystalline and dissolved cis-
platin. By the crystal optic properties the synthesized ra-
dioactive cisplatin get some qualities approaching a new
formed phase with crystal-hydrate modifications to the
initial compound composition.
Brake radiation of the electronic accelerator was
used for obtaining 195mPt by means of an irradiation of
gold. Extraction of gold was used for obtaining radioac-
tive cisplatin with high specific activity (about
1 Ci/mg). Nuclear reaction 197Au (γ,np)195mPt was used.
Synthesis of radioactive cisplatin is realized.
Cisplatin of a high specific activity was obtained in
the high-current electron accelerator using the nuclear
reaction 197Au(γ,np)195mPt with a threshold of 13.7 MeV.
The cross-section of the reaction 197Au(γ,np)195mPt slow-
ly increases to 100 MeV and according to the estimation
at 30 Mev energy has the value of 2 mbn [5]. The output
of 195mPt isomer is near 30%. Therefore the 197Au(γ
,np)195mPt reaction cross-section for the 30 MeV gamma-
quanta is about 0.6 mbn. The reaction 197Au(γ,2p)195Ir →
195mPt also leads to the 195mPt production [5]. The 196Au
yield in the nuclear reaction 197Au(γ,n)196Au→196Pt ex-
ceeds the 195mPt yield approximately by a factor of 1000.
The half-life of 196Au is 6.18 days. Therefore to decrease
the 196Pt concentration in the process of radioactive cis-
platin production it is necessary to perform a repeated
gold extraction from the irradiated target. The maximum
____________________________________________________________
PROBLEMS OF ATOMIC SCIENCE AND TECHNOLOGY. 2008. № 5.
Series: Nuclear Physics Investigations (50), p.198-202.
198
specific activity of 195mPt can be 100 Ci/mg. So, by irra-
diating the gold with bremsstrahlung during 24 hours
with the subsequent gold extraction we can obtain the
specific activity of 195mPt at a level of 2 Ci/mg that is
significantly higher than the specific activity of 195mPt
obtained by the USA researchers [4]. The gold extrac-
tion after four-hour irradiation can give the specific ac-
tivity of 195mPt at a level of 10 Ci/mg. Potentialities of
the NSC KIPT high-power electron accelerator (34
MeV and 500 µА) make it possible to produce up to 50-
100 mCi/day. To obtain 195mPt of a high specific activity
the sample of 1 g weight was irradiated with brems-
strahlung from the accelerator KUT-20 (electron energy
of 34 MeV and current of 500 µА) during 5 hours.
Platinum was separated by means of gold extraction.
For this purpose the gold sample after irradiation in the
accelerator was dissolved in the aqua regia (1:3 –
HNO3:HCl). For the more rapid dissolving we added
into the solution several drops of hydrogen peroxide. To
remove the nitrogen acid the solution was repeatedly
evaporated. Then the gold solution in the 10% hy-
drochloric acid was prepared. After 20 ml of hydrochlo-
ric acid-gold solution were poured into the extractor
(Fig.1). Into the flask, being heated up, 100 ml of ethyl
acetate were poured. By evaporating ethyl acetate was
condensed in the refrigerator and from there it arrived
via the glass pipe onto the extractor bottom. Ethyl ac-
etate was running up over the hydrochloric acid-gold so-
lution simultaneously extracting gold. Then ethyl ac-
etate got again into the heated flask with ethyl acetate.
Extraction of gold by 100 ml of ethyl acetate has been
carried out during 4 hours.
The measurement of the gamma-activity spectrum in
this stage showed significant decrease of the 196Au activ-
ity (approximately by a factor of 104). However, the rel-
ative intensity of 195mPt was insignificant. After this pro-
cedure ethyl acetate was removed and the flask was
again charged with 30 ml of fresh ethyl acetate. In this
case the extraction proceeded during 1 hour. The 196Au
activity was decreased by a factor of 10.
Subsequently, the gold extraction was repeated three
times under continuous agitation in the magnetic agita-
tor. In this case the activity of 196Au was decreasing at
each cycle by a factor of 5 and that of 195mPt by a factor
of 1.8-2. The loss of a significant amount of 195mPt at
each extraction cycle is caused by its low concentration
in the solution, namely, 7⋅10−12 mol/l of 195mPt. The total
content of platinum atoms was determined by the yield
from the reaction 197Au(γ,n)196Au → 196Pt. In our case
the total concentration of platinum atoms in the solution
was 6.4⋅10−9 mol/l. In total after two extraction cycles
we obtained 13 kBq of 195mPt that was equal to 10% of
the initial activity after irradiation in the electron accel-
erator. In Fig.2 the spectra of 195mPt solution after final
cycle of gold extraction are presented. The number of
counts, detected by the Ge(Li)-detector, of the line with
356 keV energy (196Au) makes 1.6% of the number of
K-line counts of 195mPt, that corresponds to 1.9% of the
196Au activity from the 195mPt activity.
Fig.1. Extractor of gold
100 200 300 400 500 600
channels
10
100
1000
10000
100000
co
un
ts
ju
vl
Ir192Pt195m
Au196 Ag106mKβ
Ag105
Ir192
Ag106m
Fig.2. The fragment of the γ-spectrum of the 195mPt solu-
tion after the final extraction cycle
In the spectrum of hydrochloric acid 192Ir takes
place which was produced in the reaction 197Au(γ,n
α)192Ir. The cross-section of this reaction at a gam-
ma-quantum energy of 30 MeV is less by a factor
of 3-5 than that of the reaction 197Au(γ,np)195mPt.
The yield of 192Ir after the final extraction cycle is
50% of the yield of isotope 195mPt. Proceeding from
the above-given data we can conclude that in the
hydrochloric acid solution, after finishing all the
extraction cycles, the residue of 192Ir was about
10%. Note, that its initial concentration in the solu-
tion was 4-6⋅10-12 mol/l. In addition, in the spectrum
of Fig.2 one can see a considerable amount of iso-
topes 106mAg and 105Ag from the reactions 107Ag(γ
,n)106mАg and 107Ag(γ,2n)105Аg, which are realized
in the silver impurities in gold.
In the practice of commercial 195mPt production by
the reaction 197Au(γ,np)195mPt the concentration of 195mPt
in the solution will be higher by a factor of 100-200.
Therefore, the number of cycles of gold extraction from
the solution will be less, respectively, the remaining
fraction of the isotope 195mPt in the solution will be larg-
____________________________________________________________
PROBLEMS OF ATOMIC SCIENCE AND TECHNOLOGY. 2008. № 5.
Series: Nuclear Physics Investigations (50), p.198-202.
199
er. The expected value may be 60…80%. It should be
noted that after the final extraction cycle there is 2⋅10−
7 mol/l in the solution. We suppose that further improve-
ment of the gold extraction technique will allow one to
decrease the gold concentration after the final extraction
cycle down to 10−9 mol/l.
In addition, note that the recrystallization of the ob-
tained radioactive cisplatin will allow one to decrease
considerably the gold content in the final product.
The peculiarity of the radioactive cisplatin synthesis
in our case is a small quantity of 195mPt (25 ng). The so-
lution of platinum in the hydrochlorid acid was repeat-
edly (3-4 times) evaporated on the water bath to obtain a
yellow precipitate. The dry precipitate H2[PtCl6]⋅6 H2O
was subjected to treatment with boiling water and was
evaporated again on the water bath [6,7]. Then the fresh
25% solution of potassium chloride was added to the
tenfold-water solution of platinum hydrochloric acid up
to the complete precipitation.
H2[PtCl6] + 2KCl = K2[PtCl6] = 2HCl . (1)
The yellow crystalline precipitation was obtained.
After cooling the precipitate was washed during 1.5…
2 hours with the diluted potassium chloride solution and
alcohol. The compound is crystallized in the form of
yellow octahedrons. The obtained precipitate in the 6-
7 fold quantity of water was slowly heated to boiling. In
the process, as the quantity was small, water was added
to the required volume. A 5% excess of lemon salt
(0.39 g K2C2O4⋅Н2О на 1 g K2[PtCl6]) was added to the
boiling mixture.
K2[PtCl6]+K2C2O4=K2[PtCl4]+2KCl + 2CO2 . (2)
Boiling of the solution during 1 hour does not resulted
in the formation of red-crimson precipitate. Therefore
once more portion of K2C2O4 was added. After boiling
during 1 hour the red-crimson precipitate was formed.
The obtained solution of potassium chloroplatinite
K2[PtCl4] with addition of a necessary quantity of 20%
solution of ammonium acetate (CH3COONH4) and
potassium chloride was boiled during 1.5 hours with
water replenishment. After cooling the precipitate of Pe-
jrone salt of canary color was precipitated.
K2[PtCl4] + 2CH3COONH4 = (NH3Cl)2Pt +
2CH3COOK + 2HCl . (3)
3. BIOLOGICAL TESTS
The response of tumor cells on the action of initial
and radioactive cisplatin can reflect their sensitility to
the chemicals action and to the radiation effect that is
very important in the case of antitumor therapy of pa-
tients.
Experiments were carried out to investigate the in-
fluence of initial and radioactive cisplatin on the Ehrlich
adenocarcinoma cells. The cell concentration was
1.8·106cells/ml. The cell vitality was 98%. The estima-
tion of the Ehrlich adenocarcinoma cell vitality after
staining with trypan blue was made using the light mi-
croscopy in dynamics in 1, 2, 4, 6, 12, 18, 24 and 48
hours. The cells were counted in the Goryaev chamber
under the microscope MBB-1 (x900).
The introduced dose of initial cisplatin was
7.5µg/ml, of radioactive cisplatin − 0.017 pg/ml and
0.17 pg/ml [7]. We introduced into every sample
0.03 ml penicillin that corresponded to 180 units, and
0.03 ml streptomycin that corresponded to 300 µg. The
samples were stayed in the thermostat at a temperature
of 37° for incubation.
The size of tumor cells was measured on the polar-
ization microscope (x200) before cytostatic intro-
duction. The cell size was 0.015 mm. After incuba-
tion during 12 hours the cell size was 0.010…0.015
mm with initial cisplatin and 0.005…0.007 mm
with radioactive cisplatin.
Fig.3. Effect of high-active cisplatin on the Ehrlich
cells, 60 min, 0.017 picograms
Fig.3 demonstrates the vital and dead Ehrlich ade-
nocarcinoma cells treated with radioactive cisplatin
in dose of 0.017 picograms after incubation during
60 minutes. In the field of vision one can see the vi-
tal (unstained) cells and dead (stained with blue)
cells. It should be noted that after the radioactive
cisplatin action in dose of 0.017 picograms during 1
hour the number of vital cells slightly exceeds the
number of dead cells.
Fig.4. Effect of high-active cisplatin on the
Ehrlich cells, 120 min, 0.017 picograms
Fig.4 shows the vital and dead Ehrlich adenocarci-
noma cells after introduction of cisplatin in dose of
0.017 picograms and incubation during 2 hours. It
is seen that in the field of vision the number of dead
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PROBLEMS OF ATOMIC SCIENCE AND TECHNOLOGY. 2008. №5.
Series: Nuclear Physics Investigations (50), p.198-202.
200
cells is significantly larger relatively to the number
of vital cells.
Fig.5 presents the picture of Ehrlich tumor cells af-
ter action of radioactive cisplatin in dose of 0.17
picograms. One can see that already under radioac-
tive cisplatin action during 1hour in such dose al-
most all the cells are dead. The rest vital cells coa-
lesce in coarse conglomerates. Most of them are de-
formed. A lysis state of cells is observed. Also, as a
result of the cell membrane damage the cytoplasm
escape into the intercellular space. Thus the rest vi-
tal cells lost their capability to divide.
Fig.5. Effect of high-active cisplatin on the Ehrlich
cells, 60 min, 0.17 picograms
After action of radioactive cisplatin in dose of 0.017
picograms during 6 and 12 hours in the field of vision
we observed solitary cells in the state of pyknosis, as
well as, deformed cells, sometimes, of a giant size. The
presence of giant cells and normal cells simultaneously
evidences on the probability that in future the cells will
coalesce in conglomerates. The fact that the cell prolif-
eration decreases is confirmed by investigation dynam-
ics where the inverse relationship between the cell vol-
ume increasing and their number in the conglomerate is
observed.
Apoptotic bodies were revealed in 18 and 24 hours.
A feature of cell apoptosis morphology consists in the
appearance of a great number of small-size apoptotic
bodies among many dead and vital cells.
After radioactive cisplatin action during 24 hours it
is seen that the giant cells disappear, likely, they are dy-
ing. One of possible mechanisms of cell death may be
the cell inability to withstand the osmotic pressure or to
stand against the mechanical force, for example, to the
squeeze in the instant of conglomerate formation [8].
Experiments showed that during the first hours of
incubation there was not a total death of cells under
the action of both the initial and radioactive cis-
paltin in dose of 0.017 picograms. It means that the
cells have different resistance and sensitivity to the
action of such factors as radiation and pharmaceu-
tics.
Investigation of the dose effect (cisplatin concentra-
tion from 0.01 to 0.17 picogram) on the tumor cell
vitality has shown that the increase of radioactive
cisplatin dose leads to the higher content of cells
with changes typical for necrosis. In the case of
necrosis the changes may be in the form of pykno-
sis and lysis. The cell swelling and distinct destruc-
tive changes attract attention. Then the cell mem-
brane is damaged and the cytoplasm contents
spreads into the intercellular space. Examination
shows that at doses of radioactive cisplatin of 0.17
picograms in the field of vision a great number of
cells are in the state of apoptosis. The morphologi-
cal apoptosis leads to the cell volume decreasing,
cell shrinkage and apoptotic corpuscles formation.
Apoptotic corpuscles in the form of spherical for-
mations are easily identified. They can be revealed
in groups. If they are lonely, in this case they are
surrounded light aureole.
1 2 3 4 5 6
0
20
40
60
80
0 2 4 6 8 10
0
2
4
6
8
10
V
ia
bi
lit
y,
%
Time after Cisplatin treatment, hours
7.5 microgram/ml cisplatin
0.017 picogram/ml radioactive cisplatin
0.17 picogram/ml radioactive cisplatin
197Au(γ ,np)195mPt
Fig.6. Action of initial and radioactive cisplatin on
the Ehrlich adenocarcinoma cell vitality
Fig.6 shows the Ehrlich adenocarcinoma cell vitali-
ty after introduction of initial and radioactive cis-
platin obtained from the radioactive gold target and
subsequently synthesized. As is seen from the fig-
ure the Ehrlich adenocarcinoma cell vitality under
the initial cisplatin action decreases from 78% after
1 hour to 25% after 6 hours of incubation. Under
action of radioactive cisplatin in dose of
0.017 picograms a similar dependence is observed.
The vitality of tumor cells under action of radioac-
tive cisplatin during 1hour is 54% and after 6 hours
it is 3%. It should be noted that during a short peri-
od after introduction of radioactive cisplatin in dose
of 0.17 picograms the certainly irreversible tumor
cell inhibition takes place. In the dynamics of in-
vestigations the cells reveal the loss of potency for
the unlimited reproduction, may be even with a
short-time retaining of the morphological continu-
ity. One can see that in the initial incubation period
(2-6 hours) the number of vital cells with radioac-
tive cisplatin is less than that of those with initial
cisplatin. Later we observed a significant difference
in decreasing the number of vital cells under
action of radioactive cisplatin relatively to the ini-
tial cisplatin.
The doses of radioactive cisplatin absorbed by dif-
ferent organs of animals were measured. The cisplatin
molecule containing 195mPt may have an important thera-
peutic application. Therefore, it is necessary to have an
information and reliable estimate of absorbed doses for
different organs and tissues in order to perform the fur-
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Series: Nuclear Physics Investigations (50), p.198-202.
201
ther calculation of effective doses for patients, which
will be treated with cisplatin containing 195mPt.
The experiment was carried out on animals (white
mice, males, weight of 18 g). Radioactive cisplatin
in dose of 13 kBq was intraperitoneally injected
into the animals. After injection of radioactive and
synthesized cisplatin all the animals were living.
The absorption dose (mGy/MBq) from 195Pt was
measured in different organs (kidney, liver, spleen,
bowels, seminal glands, urinary bladder wall, skin).
The controlled organs from 10 animals were
weighted and placed in the aluminum container in-
stalled on the Ge(Li)-detector for the absorbed dose
recording. The data obtained have shown that the
highest absorption dose of 195mPt-cisplatin is record-
ed in the liver (0.72±0.23); kidney (0.40±0.07);
seminal glands (0.55±0.15); spleen (0.35±0.05);
urinary bladder wall (0.25±0.02); skin (0.21±0.04).
CONCLUSIONS
1.Irradiation of cisplatin pharmaceuticals in the elec-
tron accelerator was carried out. Optimum condi-
tions for cisplatin irradiation were determined to
reach a maximum specific activity of 193m,195mPt. The
specific activity of radioactive cisplatin equal to
250-100 Bq/mg was obtained.
2.Optimum conditions for gold irradiation in the
electron accelerator for 195mPt production were deter-
mined.
3.The method of gold extraction for 195mPt produc-
tion was developed.
4.The effect of initial and radioactive cisplatin with a
high specific activity (~1Ci/mg) on the suspension
of Ehrlich adenocarcinoma cells was investigated.
The change of cell morphology depending on the
dose of initial and radioactive cisplatin was ob-
served.
5.Necrosis and apoptosis processes leading to the
death of cells are revealed under action of radioac-
tive cisplatin in dose of 0.017 picogram/ml, which is
less in 107 times then the introduced dose of initial
cisplatin.
6.The dose of absorption (mGy/MBq) from 195mPt
was measured in different organs (kidney, liver,
spleen, bowels, seminal glands, urinary bladder wall,
skin). The data obtained have shown that the highest
absorption dose of 195mPt-cisplatin is recorded in the
liver, kidney, seminal glands, spleen, urinary bladder
wall, skin.
The work is done with the STCU support, grant
№1768.
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Статья поступила в редакцию 24.09.2007 г.
ОЦЕНКА ПОГЛОЩЕННЫХ ДОЗ СИНТЕЗИРОВАННОГО ЦИСПЛАТИНА
НА ОСНОВЕ 195mPt В РАЗЛИЧНЫХ ОРГАНАХ ЖИВОТНЫХ
Н.П. Дикий, А.Н. Довбня, Ю.В. Ляшко, Е.П. Медведева, Д.В. Медведев, В.Л. Уваров, Л.Д. Грицан, Н.И. Онищенко
Проведены эксперименты по выделению изотопа платины 195mPt в реакции 197Au(γ,np)195mPt на линейном ускорителе электронов для
энергии 40 МэВ при токе 10 мкА. Разработана технология выделения 195mPt из мишени золота в экстракторе типа Кучера-Штоля. Следу-
ющий этап технологии заключался в получении синтетического цисплатина на основе 195mPt. Примесь 196Au в синтезированном циспла-
тине составила 1,4% от активности 195mPt. Измерены эффективные дозы поглощения на единицу активности от 195mPt в различных орга-
нах животных, которым был введен радиоактивный цисплатин в дозе 13 кБк. Показано, что дозы поглощения от 195mPt для различных
органов составляли от 0,72 до 0,20 мГр/MБк.
ОЦІНКА ПОГЛИНЕНИХ ДОЗ СИНТЕЗОВАНОГО ЦИСПЛАТИНУ
НА ОСНОВІ 195mPt У РІЗНИХ ОРГАНАХ ТВАРИН
М.П. Дикiй, А.М. Довбня, Ю.В. Ляшко, О.П. Медведєва, Д.В. Медведєв, В.Л. Уварoв, Л.Д. Грицан, М.І. Онищенко
Проведено експерименти по виділенню ізотопу платини 195mPt у реакції 197Au(γ,np)195mPt на лінійному прискорювачі електронів з
енергією 40 МеВ і струмом 10 мкА. Розроблено технологію виділення 195mPt з мішені золота в екстракторі типу Кучера-Штоля.
Одержано синтетичний цисплатин на основі 195mPt. Домішка 196Au у синтезованому цисплатину склала 1,4% від активності 195mPt.
Виміряні ефективні дози поглинання на одиницю активності від 195mPt у різних органах тварин, яким був уведений радіоактивний
цисплатин у дозі 13 кБк. Показано, що дози поглинання 195mPt цисплатина для різних органів становили від 0,72 до 0,20 мГр/MБк.
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PROBLEMS OF ATOMIC SCIENCE AND TECHNOLOGY. 2008. №5.
Series: Nuclear Physics Investigations (50), p.198-202.
202
PACS: 29.17.+w
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