In this laboratory, you will prepare the radioactive
pharmaceutical, Technetium-99m Sulfur Colloid Injection (99mTc-SC).
This product is used in nuclear medicine to help diagnose diseases
of the liver, spleen, and bone marrow which comprise the major
organs of the reticuloendothelial system (RES). These organs contain
arterial and venous sinuses lined with phagocytic cells that are
responsible for removing foreign particles from the blood, including
radioactive colloids. Thus, intravenous administration of 99mTc-SC
will result in localization of radioactivity in these organs,
providing a means to evaluate their morphologic and functional
status by radiation detection methods.
The radioactive colloid is produced by reacting
Tc-99m sodium pertechnetate (Na99mTcO4)
with an acidified solution of sodium thiosulfate in the presence
of gelatin. It is believed that during the reaction a small amount
of hydrogen sulfide is produced which reacts with the trace quantity
of pertechnetate to yield insoluble technetium heptasulfide. The
technetium heptasulfide then co-precipitates with the elemental
sulfur particles released by the acid hydrolysis of thiosulfate.
The following reactions are proposed to occur:
Correct organ localization of radioactivity
is predicated on the Tc-99m being bound to the colloidal particles.
If incomplete radiolabeling occurs, some of the Tc-99m will remain
unreacted in solution as Tc-99m pertechnetate ion (99mTcO-4).
This represents a radiochemical impurity which is undesirable
since its biologic distribution is different from Tc-99m bound
to sulfur colloid. Significant free pertechnetate ion (> 5%)
will localize in the thyroid gland and stomach creating unnecessary
radiation dose to the patient. Stomach localization of radioactivity
is also a problem because it interferes with the evaluation of
liver radioactivity due to the close proximity of these organs
in the body. The radiopharmacist checks for Tc-99m pertechnetate
impurity using radiochromatography. A simple and accurate technique
involves spotting a sample of 99mTc-SC on a strip of
chromatography medium (paper or thin layer) which is then developed
in a solvent, dried and cut in half for analysis. The 99mTc-SC
remains at the origin (bottom half) because of its insolubility,
but the soluble pertechnetate ion migrates to the solvent front
(top half). Each half is counted in a gamma scintillation counter
and the percent activity bound to sulfur colloid determined. The
USP limit is not less than 92% activity as 99mTc-SC.
Another potential problem with 99mTc-SC
is the precipitation of the colloid caused by an excess of aluminum
ion in the Tc-99m pertechnetate solution. The radiopharmacist
can test for the presence of aluminum ion in the Tc-99m pertechnetate
solution by a spot test method. With this method a piece of filter
paper which is impregnated with aurintricarboxylic acid (aluminon)
is spotted side by side with a sample of standard aluminum ion
solution containing 10 µg Al3+ per ml and a sample
of Tc-99m pertechnetate. Aluminum ion reacts with aluminon to
form a pink colored lake with the intensity of color directly
proportional to the amount of A13+. Since the official
limit is not more than 10 µg A13+ per ml of Tc-99m
pertechnetate solution, a comparison of the two spots provides
evidence for a pass/fail type test.
Since 99mTc-SC is to be injected
intravenously, the product must be sterile and pyrogen-free. Therefore,
the radiopharmacist must exercise good aseptic technique during
the radiolabeling procedure to minimize contamination. This primarily
means that rubber closures on vials must be cleansed with 70%
alcohol prior to transfer of sterile solutions from one vial to
another. Of course, sterile needles and syringes must be used.
If unprotected needles drop or touch non-sterile surfaces they
must be discarded. If opened vials of sterile solutions are used,
then transfers should ideally be made in a properly functioning
laminar air flow hood. For radioactive substances the hood should
be of the vertical flow exhausting type.
Frequently, parenteral solutions, including
radiopharmaceuticals, are sterilized by membrane filtration, i.e.,
filtering the non-sterile solution through a sterile 0.22 µm membrane.
This method should NOT be used for sterilizing parenterals
that contain dispersed particles such as colloidal dispersions.
The particle size of colloids is frequently larger than the pore
size of the membrane and the active ingredient will be removed
by the filter. 99mTc-SC is an example of a radiopharmaceutical
that should NOT be sterilized by membrane filtration.
For this reason the product is prepared aseptically using presterilized
reagents supplied as a kit.