J.L. Vučina, Lj.Vuksanović, R.Dobrijević Laboratory for Radioisotopes Vinca Institute of Nuclear Sciences 11001 Belgrade. P.OBox 522, Yugoslavia

Abstract: Given is a short review on the production of radionuclides which was performed in the VinČa Institute of Nuclear Sciences by using the nuclear reactor RA. Regarding the considerations of the possible re-starting of this reactor its use for the production of medical radionuclides should be taken into account. Listed are some of the important medical radionuclides routinely produced in nuclear reactors in the world and discussed the conditions for their obtaining in the reactor RA.

Key words: Nuclear reactor, Radionuclides,

INTRODUCTION After the discovery of by Hahn and Strassmann in 1938 and the first self-sustaining nuclear chain reaction demonstrated by Fermi and coworkers in 1942 the permeation of reactor-produced radionuclides in nearly all fields of science was fast. Already in 1946 the first such radionuclides became available for public distribution. The pioneering role in the production and the distribution of radionuclides for medical and biological reasearch played the Oak Ridge National Laboratory (ORNL). The peacetime shipments of radionuclides became usual. Soon large activities of radionuclides in the elemental and in the form of labeled compounds were on disposal. Among the first there were the long lived beta emitters 3H, "C, 35S, 32P and ,2SI. The availability of these and afterwards many other radionuclides, the development of labeling techniques and the introduction of scintillation counters and scanners made the tracer technique particularly in nuclear medicine and an essential tool in the routine practice. The development of the radionuclides production in the Vinca (former "Boris Kidrič") Institute of Nuclear Sciences begun in 1956 together with the programm of the construction of the heavy- nuclear reactor RA. This program was realised in three years and the first chain reaction was demonstrated on November 29, 1959. The reactor RA was operating till the mid seventies. In the frame of the discussions about its eventual re-starting its capability for the production of radionuclides should also be considered. This paper brings a short review about the production of radionuclides for the use in nuclear medicine performed in the Institute. Listed are some the radionuclides which are now routinely produced in the world and are currently applied in nuclear medicine for diagnostics and . Some predictions regarding the possible production of some of them in the nuclear reactor RA are also revealed.


After the begirming of the operation of reactor RA the production procedures of many radionuclides were developed. In 1959 the HOT Laboratory was founded which included also the Department for the production of radioisotopes in which most of these investigations were performed. At the end of sixties there were already about 70 radioactive products with 25 radionuclides in routine production (1). By using the targets in the form of carbonates produced were radionuclides like 24Na, 42K, ASCa and wSr. *°Co, "Zn and U0Ag were obtained by of metal targets while oxides were applied for the production of ^e

545 and "'Ce. The processes of the separation of the desired radionuclide from the irradiated material were relatively simple consisting of dissolution, filtration, etc. However, their specific activities were usually low due to the presence of carrier. For special applications, particularly in nuclear medicine, radionuclides of high specific activities are required. Such production is much more complicated. Several such procedures were developed in the Institute. Most of these very important radionuclides are still routinely produced and applied in the world. The basic data about some of these radionuclides, together with their possible applications are given in Table 1.

Table 1: Some of the most important radionuclides for the application in medicine and biology produced in the nuclear reactor RA a) Nuclear reaction (n,y) Radio• Mode of decay. Target Uses Ref. Energy (MeV)

24Na p-(E*„=1.390) Na2C03 Hypertension research 1,2 (15 h) y(1.370; 2.750 Cancer treatment, cell P O P(E =1.710) metabolism, production of 3 (14.3 d) 2 5 mM To assess reed blood cells slCr Cr 0, EC 2 survival studies, Production 4 (27.8 d) Szilard- Chalmers y (0.320) of radiopharmaceuticals

59 58 Fe Fez03 PXE^^eo) Biochemistry research tracer 2 (44.6 d) (enriched target) Y (0.192; 1.099; 1.291) 75Se 74Se EC Protein studies 2 (120 d) (enriched target) Y (0.121; 0.135; 0.264)

"Mo PtE^l.39); 99n Mo03 To produce Tc 5 (66.6 h) y (0.181; 0.739) Thyroid diagnostics and 131J TeC) (3-^=0.61); 2 therapy, production of 6 (8.06 d) HJeO, y (0.364) radioph armaceuticals ™Hg EC Production of renal HgO 7 (46.59 d) Y (0.279) 198Au PXE^O.960); Au Therapy of cancer 8 (2.69 d) Y (0.411) b) Nuclear reaction (n,p) Cancer treatment, cell

MgS04 3-^=1.710) metabolism, production of (14.3 d) 9 radiopharmaceuticals

3S Biology, studies of cell S KC1 p-(EmK=1.710) metabolism, production of 10 (87.1 d) labelled compounds


Regarding the reactor-driven production of medical radionuclides performed in the world some comments can be given.

546 As it can be seen from Table 1 the production which was performed in nuclear reactor RA included both the radionuclides for diagnostics and therapy in nuclear medicine. The listed radionuclides are still in use except ^Hg which was abandoned in favour of other radionuclides with more suitable physical characteristics. However it is still produced but found some other application e.g. as the calibration source. Already for years the most important diagnostic radionuclide is WmTc. Its favourable physical characteristics and diverse chemistry enabled the development of many radiopharmaceuticals targetring different organs and tissues in human body. Other reactor- produced diagnostic radionuclides in common use are 125I,mI and 13JXe. The main source of "Tc are "MO/99MTC generators. The parent is produced almost exclusively by fission. The former method by using (n,y) nuclear reaction, applied also in Yugoslavia (5), is abandoned due to low of the produced "Mo. Some other radionuclides are on large scale also obtained by the separation from the products of uranium fission ("Sr, ,33Xe). The very important radionuclide 131I can be in high activities routinely obtained both from fission and by activation of . In the therapy there is no such a predominant radionuclide as it is ""Tc in the diagnostic nuclear medicine. Here the choice of a radionuclide depends not only on its physical and pharmacokinetic properties and the in-vivo localization. It depends in great deal also on the nature, size and radiosensitivity of the tumor. The proximity of the tumor to -sensitive normal tissue should also be considered. Some of radionuclides for the application in therapy are listed in Table 2.

Table 2: Reactor-produced radionuclides of high specific activities for the application in therapy in nuclear medicine

Radionuclide Mode of decay Nuclear reaction Uses (T„) Energy (MeV)

65 Cancer therapy; Labelling of antibodies 61Cu (2.4 d) Zn(n,p) ME^O.57) y (0.184 for cancer therapy P^E^.ĆS) "As (1.6 d) *Ge(n p) Cancer therapy iyi Y (0.319)

1IO p-tE^l.OS) 111 Ag (7.5 d) Pd(n,Y,P) Cancer therapy Y (0.342)

131 13& p-(*W"0.81) Diagnostics and thyroid disorders I (8.05 d) Te(n,y,P) Y (0.364) including cancer treatment

177 p-(EmflX=0.5) Cancer treatment and labelling of Lu (6.7 d) 176Yb(n,y,p) y(0.20S) antibodies for cancer therapy KB«M).46) Cancer therapy; '"Au (3.2 d) 198Pt(n,y,P) Y (0.158) Treatment of rheumatoid arthritis Decays to "Y which is used in cancer *Sr (28.6 a) Fission of p-(E =2.27) max therapy

188 l88 186 ls7 Decays to Re which is used in cancer W (69.4 d) W(n,y) W(n,Y) p-(E =2.1) max therapy

So the field of the therapeutic reactor-produced radionuclides is potentially very large. In short, the main categories of radionuclides for the eventuall use in therapy are: 1. Bone agent to reduce pain (""Sr, 186Rh, l88Rh, 153Sm, U7Sn) 2. Estrogens labelled by "Br or 131i for treatment of hormone-dependant cancers 3. Colloids for synovectomy (,65Dy, ,66Ho, "Y, l03Pd) 4. Monoclonal antibodies and tissue-specific peptides for cancer treatment (I25I ml "Y MCu) ' '


Nuclear reactors offer good possibilities of the production of radionuclides for nuclear-medical applications. In principle the radionuclides of interest could be produced either directly by some of the nuclear reactions given in Tables 1 and 2 or by using generator systems. Some of them are also given ("Mor-'Tc, '"Sr/^Y, ,88W/188Re). The most important diagnostics radionuclide is "Tc which is obtained by using 99Mo/"mTc generators.. The parent "Mo is almost exclusively produced by its separation from the products of uranium fission. Some other radionuclides (I31I, '"Sr, etc) are also obtained from uranium fission. For such a production in the nuclear reactor RA and particularly for the further purification there are no conditions. The other important radionuclide which is used both in diagnostics and therapy - i3,I could be however routinely obtained also by neutron activation of tellurium. Also possible is the production of some other radionuclides like 51Cr, 1251, 127Xe, some parents for the generator systems, etc. Particularly a potentially broad field of the reactor production are the radionuclides used for therapy. Some radionuclides (e.g. ^Co) could be produced either in the form of a radiochemical or in the form of the sealed radiation source. In general the nuclear reactor RA could be used for the production of a selected number of radionuclides both for the nuclear medicine and other applications. The choice depends on the parameters of the reactor and the potential market for the given radionuclide. In any case further investments in the whole production process ( target preparation, irradiation, chemical processing of the irradiated target and the production and quality control of the obtained radionuclides and labelled compounds) are necessarry.


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