PRODUCTION OF RADIONUCLIDE PRODUCTION OF RADIONUCLIDE 2/27/2016 L5,L6 and L7 1 PRINCE SATTAM BIN ABDUL AZIZ UNIVERSITY COLLEGE OF PHARMACY Nuclear Pharmacy (PHT 433 ) Dr. Shahid Jamil

Artificial radionuclides are derived by bombardment of stable target nuclei with neutrons, usually in a nuclear reactor, or with other particles in cyclotrons and by isolation from the spent fuel from nuclear reactors. Production of radionuclides 2/27/20162 L5,L6 and L7

A variety of radionuclides are produced in nuclear reactors. 1. Nuclear Reactors (Nuclear piles) 2/27/20163 L5,L6 and L7

2/27/2016 L5,L6 and L7 4 The nuclear reactor constructed of Fuel Rod : made up of fissile materials such as enriched 235U and239Pu Control rod (cadmium ) remove the excess neutron by absorbing the thermal neutron. Moderator (low molecular weight material such as water, heavy water, beryllium, and graphite,) to slow down the reaction. These fuel nuclei having fissile materials undergo spontaneous fission with extremely low probability

(fragments)قطعة or كسرة, انفلاق or إنشطار نووي (fission) (emission)إصدار Fission is defined as the breakup of a heavy nucleus into two fragments of approximately equal mass, accompanied by the emission of two to three neutrons with mean energies of about 1.5 MeV. In each fission, there is a concomitant energy release of 200 MeV that appears as heat and is usually removed by heat exchangers to produce electricity in the nuclear power plant. 2/27/ L5,L6 and L7

2/27/2016 L5,L6 and L7 6 There are two types of interaction with thermal neutrons for the production of useful radioactive substances from the pile (nuclear reactor) 1)Fission of heavy element, those produced as fission products 2) those produced by neutron capture or (n, γ ) reaction.

(1) Those produced as fission products When a target of heavy elements is inserted in the reactor core, heavy nuclei absorb thermal neutrons and undergo fission. Fissionable heavy elements are 235U, 239Pu, 237Np, 233U, 232Th and many other element having atomic number more than 90. Nuclides produced by fission may range in atomic number from about 28 to nearly 65. 2/27/20167 L5,L6 and L7

2/27/2016 L5,L6 and L7 8 These isotopes of different elements are separated by appropriate chemical procedures that involve precipitation, solvent extraction, ion exchange, chromatography, and distillation. The fission radionuclides are normally carrier-free or NCA, and therefore isotopes of high specific activity are available from fission. Since the chemical behavior of isotopes of many different elements is similar, contamination often becomes a serious problem in the isolation of a desired radionuclide; therefore, meticulous methods of purification are needed to remove the contaminants

Those produced as fission product. The following reactions illustrate one of many combinations fission reactions which are possible U + n Sn + Mo + n + n The 131 Sn and the 106 Mo are very radioactive and have very short half-lives. They immediately decay by a series of beta decay processes 2/27/20169 L5,L6 and L7

Sn Sb Te I Mo Tc Ru Rh Both 131 I and 106 Rh are available commercially as fission produced isotopes. Before use they must be separated chemically from a large number of other fission-produced radioisotopes. For many of the isotopes produced by fission, separation is too difficult or costly; hence, the majority of radioactive compounds are prepared by neutron activation. 2/27/ L5,L6 and L7

Neutron activation may result from several types of reaction: a- The neutron capture or the (n, γ ) reaction. This involves the capture of thermal neutrons by the target nuclei to yield a radioactive compound nucleus, which is in an excited state due to the binding energy liberated by the capture of a neutron. This surplus energy is emitted as g- radiation Na + n Na + γ P + n P + γ /27/ L5,L6 and L7

The process usually does not yield material of high specific activity since the product is chemically identical to the target and 32 P 15 is diluted with the stable 31 P 15 so cannot be separated from it. 2/27/ L5,L6 and L7

b- Transmutation process or the (n, p) reaction. These reactions involve the loss of heavy particles. In these reactions protons or α - particles are emitted from the compound nucleus following neutron absorption. Fast neutrons may be required for these reactions to occur, since considerable energy is needed to expel the heavy particle. Examples S + n P + P In such cases the product is chemically different from the target and can be separated in very high specific activity. 2/27/ L5,L6 and L7

The cyclotron and similar particle accelerators can be used only with charged particles such as electrons, protons, deuterons and α particles because the operation of such machines depends upon the acceleration of these particles by magnetic and/or electrostatic fields with the charge (either + or-) to a high velocity. 2. Cyclotron - Produced Isotopes 2/27/ L5,L6 and L7

When the particles have been accelerated to a high velocity, even approaching the velocity of light and representing enormous energies, they are caused to strike a target containing the atoms to be bombarded. 2/27/ L5,L6 and L7

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22 Na is prepared in this way by the interaction of high - velocity deuterons with magnesium. The nuclear equation is: 24 Mg D 1 22 Na α 2 2/27/ L5,L6 and L7

Other medically important nuclides which have been produced in a cyclotron by use of high-energy deuterons include 11 C, 13 N, 15 O. Those which have been produced using high- energy alpha particles include 18 F, 43 K High- energy protons have been used to produce 132 I, 127 Xe, 201 Pb and 203 Pb cyclotron production of some medically useful nuclides. 2/27/ L5,L6 and L7

When clinical tests require that a radioisotope be administered internally, it is advantageous to use an isotope with a short half-life to minimize the radiation dose received by the patient. One of the most significant advances in radiopharmaceuticals is the use of generators for the production of short half - life radiopharmaceuticals. 3. Generators 2/27/ L5,L6 and L7

Generators ("cows") are either ion exchange resins or alumina columns which upon which adsorbed a long lived parent radionuclide. With time, the parent radionuclide decays to a daughter radionuclide that is not adsorbed on the column by eluted or milked from the column by an eluant in which the parent nuclide has no solubility but soluble the daughter nuclide. 2/27/ L5,L6 and L7

Example: Technetium -99m ( 99m Tc), which is obtained from a generator constructed of molybdenum-99 ( 99 Mo) adsorbed to an alumina column. Molybdenum-99 decays with 66 hour half- life to technetium- 99m. 2/27/ L5,L6 and L7

The technetium-99m is eluted (or milked) from the column with normal saline solution. The 66 hour half- life of molybdenum-99 provides sufficient manufacturing time for once weekly preparation. Elution of the generator on a daily basis, by the nuclear pharmacist, provides technetium - 99 m for the preparation of radiopharmaceuticals. 2/27/ L5,L6 and L7

Characteristics of a number of parent-daughter systems which have been used in radioisotope generators: ApplicationHalf-life Daughter isotope Half-life Parent isotope Cancer therapy 64 h 90 Y 28 y 96 Sr Thyroid scanning 2.3 h 132 I 3.2 d 132 Te Bone scanning 2.8 h 87m Sr 80 h 87 Y Kidney function 1.7 h 113m In 118 d 113 Sn 2/27/ L5,L6 and L7