Pharmaceutical Manufacturing Handbook: Production and

82 RADIOPHARMACEUTICAL MANUFACTURING
Pure α and β emitters are easy to shield, and thus production involving these can
be performed in sealed production units with no lead protection. One must keep in
mind, though, the potential hazard when inhaling some of these materials. Moreover,
many radionuclides used for radiotherapy have an additional γ component.
Hence, local lead shielding may be necessary. If the γ component is larger or represents
very high energy emission, a total lead shielded unit may be necessary. The
latter will be the case when manufacturing 131 I radiopharmaceuticals for therapy,
since 131 I is a radionuclide consisting of a high - energy γ photon together with the β
component.
Radiopharmaceuticals for therapeutic use must have a high target - to - background
ratio. Targeted radiotherapy involves the use of molecular carrier such as a
receptor - avid compound or an antibody to deliver a radionuclide to cell
populations.
A challenge when performing radiolabeling of carrier molecules for targeted
radiotherapy is the potential risk of radiolysis due to the radiation characteristics
of the radionuclides involved. When increasing the specifi c activity, as part of the
scaling up, the risk of radiolytic decomposition of the labeled compound also
increases. This is particularly pronounced when using α emitters. The addition of
stabilizers in the form of scavengers can reduce this risk. Benzyl alcohol is an
example of a compound that acts as a scavenger by catching up with free radicals
in the solution.
Another approach is to use kit formulations also for this kind of product. Therapeutic
radiopharmaceuticals have been developed where the carrier molecule is
formulated in a lyophilized kit and supplied together with the radionuclide. An
example of this is the MAb ibritumomab tiuxetan formulated for labeling with the
β - emitting radionuclide 90 Y. Yttrium - 90 ibritumomab tiuxetan (Zevalin) is used in
the treatment of non - Hodgkin ’ s lymphoma (NHL).
The labeling is performed in a centralized radiopharmacy, hospital radiopharmacy,
or nuclear medicine department immediately before use.
Radioactive Sanitary Products Radioactive sanitary products could be considered
as radiopharmaceuticals according to the defi nition given in directive 2001/83/
EC, although there are signifi cant differences between radioactive sanitary products
and classical radiopharmaceuticals. The former can in fact be considered as
encapsulated radioactive sources, although with the use of microencapsulated sanitary
products (such as micrometer - sized glass or polymer beads loaded with a
radionuclide), the difference between both types is becoming more diffi cult to
establish.
In any case, radioactive sanitary products are delivered locally (and not systemically
or orally) for the local treatment of a disease. The idea is to give a high dose
of radiation to a specifi c part of the body by the implantation of the corresponding
sanitary product in the desired zone. The sanitary product must not be metabolized,
destroyed, or removed from the place it has been located during a suffi ciently long
time as to give the desired high radiation dose.
The most commonly used radioactive sanitary products are millimeter - sized
seeds or needles loaded with 103 P, 192 Ir, 90 Sr, or 125 I. Currently micrometer - sized or
even nanometer - sized beads loaded with 90 Y are being used for the treatment of
specifi c diseases.