Pharmaceutical Manufacturing Handbook: Production and

PRODUCT MANUFACTURING 75
tainer. The name of the radiopharmaceutical, including the radionuclide, together
with the amount of radioactivity in the vial at a stated calibration time is part of the
necessary information. So is the expiry date of the product. Furthermore, the symbol
for radioactivity, designed as a black propeller, is obligatory on labels for radioactive
solutions.
When the products are intended for distribution and transport, the packaging
and labeling of the outer packages must be done according to the national regulation
of the country from which the shipments will depart, transfer, and arrive. The
outer packaging material must be properly tested in accordance with the type of
shipment, most frequently type A packages for radiopharmaceuticals. Furthermore,
the packages must be labeled with radionuclide data, such as type and amount of
radioactivity, along with the transport index (TI), which indicates the radiation from
the package at 1 m distance. While the information on the product itself (outside
the lead pot) is intended for the physicians, the information outside the package is
intended for the transport personnel.
1.3.4
PRODUCT MANUFACTURING
1.3.4.1 Production of Radionuclides
Radiopharmaceuticals are labeled with artifi cial radionuclides that are obtained by
bombardment of stable nuclei with subatomic particles or photons. Nuclear reactions
produced in such a way convert stable in unstable (radioactive nuclei). Several
kind of devices are used for such purposes, including nuclear reactors, particle accelerators,
and generators.
Various types of targets have been designed and used for both reactor and cyclotron
irradiation. In the design of targets, primary consideration is given to heat
deposition in the target by irradiation with neutrons in the reactors or charged
particles in the cyclotrons [2] . As the temperature can rise to 1000 ° C during irradiation
in both reactors and cyclotrons, the target needs proper cooling to avoid
burning. Most often, the targets are designed in the form of a foil to maximize the
heat dissipation. The target element should ideally be monoisotopic or an enriched
isotope to avoid extraneous nuclear reactions.
Nuclear Reactors Nuclear reactors are highly complex systems in which two kinds
of nuclear reactions are useful for the production of clinically useful radionuclides:
Neutrons produced by the fi ssion of heavy nuclides (such as 235 U or 239 Pu) are used
in a neutron capture (n, γ ) reaction to produce an isotope of the same element
that is bombarded by the neutrons. Such reactions can be produced almost in all
elements with different probability. Examples of useful nuclear reactions are
130 131 131 Te(n, γ ) Te (which produces I after emission of β particles with a half - life of
25 min), 50 Cr(n, γ ) 51 Cr, 58 Fe(n, γ ) 59 Fe, and 98 Mo(n, γ ) 99 Mo. The second possibility for
the use of nuclear reactors is to use fi ssion reactions (n,f) in which a heavy nuclide
is broken down into two fragments. Many clinically relevant radionuclides can be
produced from thermal fi ssion of 235 U, such as 131 I, 117 Pd, 133 Xe, and 137 Cs. The isotopes
produced by this kind of fi ssion reaction must be separated and purifi ed by appropriate
chemical procedures, but since the chemical behavior of many different heavy