Pharmaceutical Manufacturing Handbook: Production and

PRODUCT MANUFACTURING 81
Most of these preparation kits have been developed for labeling of various substances
with 99m Tc. Labeling is normally a single - or two - step procedure consisting
of adding a solution of 99m Tc - pertechnetate to the preparation kit. The preparation
kit contains the ingredient necessary for labeling, such as the substance or ligand to
be labeled, a reducing agent, buffers for pH adjustments, and various stabilizers. The
reducing agent, very often a stannous salt, is added to bring the radionuclide into a
valence state with high reactivity.
Most preparation kits are lyophilized, and the reason for this is to extend the
shelf life of the products. Some preparation kits can in fact be stored for more than
one year. Since these products are not radioactive, conventional clean rooms and
clean - room technology can be applied for production of preparation kits. Most of
these products have to be produced aseptically, as they cannot be sterilized with
other methods. During lyophilization of the preparation kits used for 99m Tc labeling,
it is very important to remove all the oxygen from the kit vial. This is to ensure the
right valence of the tin salt. Normally, the vials are fi lled with an inert gas, such as
nitrogen, before the vials are closed completely. It is important, though, that the gas
is dried. Some manufacturer chose to not completely replace the removed oxygen,
giving a slightly negative pressure inside the kit vial. This may be favorable for the
kit - labeling procedure.
Therapeutic Radiopharmaceuticals Radiopharmaceuticals used for therapy
(radiotherapy) are designed such that, after administration, they act locally at a
target by either damaging or killing cells by irradiation. One of the attractions of
radionuclide therapy is the existence of radiation with quite different dimensions
of effectiveness, ranging from subcellular (Auger electrons) to hundreds of cell
diameters ( β particles). In between, α emitters have a tissue range equivalent to
only a few cell diameters [9] . Alpha emitters have a very high linear energy transfer
(LET), being very potent at short distances.
Table 2 lists a selection of radionuclides and radiopharmaceuticals used in
radiotheraphy.
TABLE 2 Selected Radionuclides and Radiopharmaceuticals Used for Radiotherapy in
Routine Use or as Part of Clinical Investigations
Radionuclide Mode of decay t1/2 Radiopharmaceuticals
131 I
90 Y
186 Re
188 Re
177 Lu
153 Sm
89
Sr
223
Ra
211
At
213 Bi
166
Ho
169 Er
165 Dy
32
P
− β
− β
− β
− β
− β
− β
− β
/ γ
/ γ
/ γ
/ γ
/ γ
α / γ
α
α
− β / γ
− β
− β
/ γ
β−
8.04 days
2.7 days
3.8 days
17 h
6.6 days
1.9 days
50.6 days
11.4 days
7.2 h
46 min
26.8 days
9.4 days
2.3 h
14.3 days
131 131 131 I - NaI, I - MIBG, I - mAbs
90 90 90 Y - colloid, Y - DOTATOC, Y - mAbs
186 186 Re - sulfi de, Re - HEDP
188 Re - HEDP
177 Lu - DOTA - Tyr3 - octreotide
153 Sm - EDTMP
89
Sr - chloride
223
Ra - chloride
211
At - mAbs
213
Bi - mAbs
166
Ho - colloid
169 Er - citrate colloid
165 Dy - ferric hydroxide macroaggregate
32 P - ortho - phosphate