Pharmaceutical Manufacturing Handbook: Production and

PRODUCT MANUFACTURING 77
practical point of view, almost 97% of the saturation activity value is reached after
irradiation of the target for fi ve half - lives of the radionuclide. Longer irradiation
times do not produce signifi cant increases in the activity obtained. Methods to
obtain several cyclotron - produced radionuclides are described below.
Iodine - 123 can be produced either directly or indirectly in a cyclotron. Direct
reactions usually lead to 123 I contaminated with other iodine radioisotopes, such as
124 I or 125 I, due to side nuclear reactions. Using nuclear reactions such as 123 Te(p,n) 123 I,
122 Te(d,n) 123 I, or 124 (p,2n) 123 I produces 123 I that is obtained after dissolving the target
in hydrochloric acid by distillation into dilute NaOH.
In the indirect methods the radionuclide produced after bombardment of the
target is not 123 I, but a radionuclide that decays to 123 I with a short half - life. The most
widely used nuclear reactions produce 133 Xe (which decays to 123 I with a half - life of
2.1 h) by bombardment with high - energy 3 He or 4 He particles or 123 Cs (which decays
to 123 Xe with a half - life of 5.9 min, and then 123 Xe decays to 123 I) after irradiation of
124 Xe with high - energy protons. Complex processing and purifi cation processes must
be used to obtain 123 I in any of these cases, and adequate design and composition
of the target are critical to facilitate the process.
Thallium - 201 is obtained using an indirect reaction such as 203 Tl(p,3n) 201 Pb in
which 201 Pb decays to 201 Tl with a half - life of 9.4 h. Thallium - 201 can in this way be
obtained pure and free from other contaminants after several purifi cation steps and
letting the target product decay for 35 h.
Indium - 111 is produced by a direct nuclear reaction by irradiation of an 111 Cd
target with 15 - MeV protons. After irradiation the target is dissolved in HCl and
purifi ed in an anion exchange column.
Positron emission tomography has become a widely used diagnostic technique in
nuclear medicine. Ultrashort half - live radionuclides are used in these cases, and such
radionuclides are mostly obtained in small cyclotrons with high yields and short
irradiation times. The overall process will be described further in this chapter when
PET radiopharmaceuticals are described.
Generators A generator is constructed on the principle of the decay – growth relationship
between a parent radionuclide with longer half - life that produces by disintegration
a daughter radionuclide with shorter half - life. The parent and the
daughter radionuclide must have suffi ciently different chemical properties in order
to be separated. The daughter radionuclide is then used either directly or to label
different molecules to produce radiopharmaceutical molecules.
A typical radionuclide generator consists of a column fi lled with adsorbent material
in which the parent radionuclide is fi xed. The daughter radionuclide is eluted
from the column once it has grown as a result of the decay of the parent radionuclide.
The elution process consists of passing through the column a solvent that
specifi cally dissolves the daughter radionuclide leaving the parent radionuclide
adsorbed to the column matrix.
The main advantage of the generators is that they can serve as top - of - the - bench
sources of short - lived radionuclides in places located far from the site of a cyclotron
or nuclear reactor facilities.
A generator should ideally be simple to build, the parent radionuclide should
have a relatively long half - life, and the daughter radionuclide should be obtained
by a simple elution process with high yield and chemical and radiochemical purity.
The generator must be properly shielded to allow its transport and manipulation.