Proceedings o f the Third Eurasian Conference “Nuclear Science and its Application”, October 5 - 8 , 2004.
APPLICATION OF RADIOISOTOPES
IN PHARMACEUTICAL RESEARCHES
Khujaev S.
Institute o f Nuclear Physics, Tashkent, Uzbekistan
INTRODUCTION
It is widely known that radioisotopes can be used in the processes of receiving radiopharmaceutical diagnostic preparations [1,2]. A radioactively labeled chemical compound, pharmacological kinetics of which allows solving specific diagnostic problems in an organism, 276
Proceedings o f the Third Eurasian Conference “Nuclear Science and its Application”, October 5 - 8 , 2004. are used in radio-pharmaceutics. Another use of radioisotopes in pharmaceutics is their application as a radioactive mark at a stage of creation of a new medical preparation. In this case, labeled radioisotope preparations are mainly used to study their pharmacological kinetics [3], Development of inclusion method of radioisotope into a chemical structure of radiopharmaceutical preparation has always been of great importance.
In the Institute of Nuclear Physics AS RU, in recent years, works are done on receiving some new medical preparations that are labeled by radioisotopes in order to study their pharmacological kinetics. These preparations are based on microelements with a complex set of properties possessing expressed biological activity and have great value in pharmaceutical science of Republic of Uzbekistan. Reception of labeled compounds of all preparations was carried out by inclusion method of a radioisotope at the stage of their synthesis.
This work presents the results of researches on synthesis of radioactively labeled preparations - Piracin, labeled by 69mZn radioisotope; Feramid, labeled by 59Fe radioisotope; Cobavit, labeled by 57Co radioisotope and VUC, labeled by 57Co radioisotope.
EXPERIMENT
69mZn and 59Fe radioactive isotopes were obtained in nuclear reactor WWR-SM by irradiating Zn(NC>3)2 samples and high pure metallic Iron in nuclear reactions 68Zn(n,y) 69mZn and 58Fe(n,y)59Fe. 57Co radioactive isotope was received in cyclotron U-150 by irradiating enriched Nickel-58 isotope in nuclear reaction 58Ni(p,pn)57Co. Irradiated samples were exposed to radiochemical processing with the purpose to purify and receive their radioactive solutions. Received radioactive solutions were used to synthesis of labeled preparations. Radiometric measurements were carried out in the nuclear gamma spectrometer NP-424L and in the measuring plant with the semi-conductor Ge(Li) detector.
Used Pyridoxine hydrochloride - B6 HC1, NaHCCh, Zn(N03)2-6H20 and radioactive solution 69mZn(NC>3)2 were as the start reagents to synthesize labeled Piracin(69mZn). As the start reagents for synthesis of labeled Feramid(59Fe) Amidine nicotinic acid, Ascorbic acid, FeCl2-4H20 and radioactive solution 59FeCl were used. For synthesis of Cobavit(57Co) Glutamine acid - HOOC- (CH2)2-CH(NH3)-COOH), Vitamin “U” - HOOC-CH(NH2)-(CH2)2-S(CH3)2Cl, Na3[Co(N02)6], NaOH and 57Co carrier-free radioactive solution were used. For synthesis of VUC preparation the reactive of vitamin “U”, C0CO3 and 57Co carrier-free radioactive solution were applied.
RESULTS
Synthesis of Piracin(69mZn). To receive radioactively labeled Piracin, radioactive isotopes 65Zn and 69mZn may be used. From the point of radioactive safety, the most suitable is 69mZn radioisotope. However, at irradiation of Zinc compounds in the nuclear reactor the both radioisotopes were formed. This is the reason why it is necessary to create such irradiation conditions that will facilitate production of only 69mZn radioisotope. It is calculated that during irradiation of 5-10 hours, the activity of 69mZn is 670-750 times higher than the activity of 65Zn.
The synthesis of Piracin(69mZn) was carried out in water-ethanol medium by the following scheme:
B6 HC1 + NaHC03 -> B6(basic) + C 02t + NaCl (1)
3 B6(basic) + Zn(N03)2 + 69mZn2+ -> 69mZn(B6)3 (N 03)2-2H20 = H20 (2) B6 - Vitamin. Yield of labeled Piracin(69mZn) preparation was 65-70%. The preparation was in the form of white powder.
Synthesis of Feramid(59Fe). To receive radioactively labeled Feramid, radioactive isotopes 55Fe and 59Fe may be used. Reception of radioisotope 55Fe, due to a long decay period, is bound a long period of time irradiation, and also this radioisotope does not have gamma-emission. In this
Section IV. Application o f Nuclear Technologies in Industry, Medicine and Agriculture
Proceedings o f the Third Eurasian Conference “Nuclear Science and its Application”, October 5 - 8 , 2004. connection 59Fe radioisotope was used. On irradiation of Iron samples in the nuclear reactor, 54Mn radioactive isotope was formed by nuclear reaction 54Fe(n,p)54Mn, as admixture. In order to separate 59Fe from 54Mn, radiochemical processing technology based on anion exchange column was used. Cleaning degree of 59Fe from 54Mn was more than 103.
The synthesis of Feramid(59Fe) was conducted by the following scheme:
C5H4N CONH2 + FeCl2 + 59Fe2+ -> C5H4NCONH2-59FeCl2 (3)
Yield of labeled Feramid(59Fe) preparation was more than 90%. The preparation is in the form of fine crystalline white-yellow powder.
Synthesis of Cobavit(57Co). To receive radioactive isotope 57Co, protons in the cyclotron irradiated enriched Nickel-58 targets. Extraction, purification and concentration of 57Co were carried out by radiochemical processing technology based on anion exchange column with resin Dowex 1x4. Following the technology 57Co carrier-free radioactive solution was received in 0,1M HC1 solution.
Synthesis of Cobavit(57Co) preparation was carried out in water-ethanol media by following scheme:
Na3[Co(N02)6] + 3NaOH + 57Co3+ -> 57Co(OH)3 + 6NaN02 (4) 57Co(OH)3+ 2[HOOC-(CH2)2-CH(NH3)-COOH] ->
-> 57Co(OH) [OOC-(CH2)2-CH(NH3)-COO]2 + 2H20 (5)
57Co(OH) [OOC-(CH2)2-CH(NH3)-COOH]2 + HOOC-CH(NH2)-(CH2)2-S(CH3)2Cl ->
-> 57Co[OOC-(CH2)2-CH(NH3)-COOH]2«[OOC-CH(NH2)-(CH2)2-S(CH3)2C1] + H20 (6)
Yield of labeled Cobavit(57Co) preparation was 70%. The preparation was in the form of brown powder.
Synthesis of VUC(57Co). The reception of radioactive solution 57Co carrier-free method is the same as in the synthesis of Cobavit(57Co). Synthesis of preparation was carried out in water media by the following scheme:
2[HOOC-CH(NH2)-(CH2)2-S(CH3)2Cl] + CoC03 + 57Co2+ -> C 0 2t + H20 +
+ 57Co[OOC-CH(NH2)-(CH2)2-S(CH3)2C1]2 (7)
Yield of labeled VTJC(57Co) preparation was more than 80%. The preparation was used as its 2% water solution. The solution was of dam-yellow color.
All receiving labeled preparations for investigation its pharmaceutical kinetics were used. REFERENCES
1. Gerasimov. N.F., Kodina, G.E., Korsunski, V.N. Razrabotka i ispolzovaniye radio- farmacevticheskikh preparatov. Itogi nauki i techniki. Ser. Radiacionnaya biologiya, tom 10. VINITI ISSN 0202-7151, Moscow 1991, s. 3-90.
2. Vserossiiyskaya Conf. 50 let proizvodstva i primeneniya isotopov v Rossii. Obninsk 20-22 Okt. 1998, Sekciya 3. Sbornik thesisov i dokladov. Obninsk 1998, s. 63-96.
3. Kholodov, L.E., Yakovlev V.P. Klinicheskaya pharmacokinetica. Moscow, “Medicina”, 1985, 485 s.
278
