Introduction

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 (Na^99mTcO₄) 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:

1.  S2O3-2 + 2H+ --> S  + SO2 + H2O

2.  2H99mTcO4 + 7H2S --> 99mTc2S7 + 8H2O

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.