Technetium ⁹⁹ᵐTc stannous agent labelled cells

At doses used for diagnostic procedures, neither stannous pyrophosphate, sodium (^99mTc) pertechnetate nor stannous pyrophosphate (^99mTc), nor labelled Red Blood Cells appear to exert any pharmacodynamic effects.

Distribution

Intravenous injection of stannous salts induces a “stannous loading” of erythrocytes. Subsequent sodium (^99mTc) pertechnetate injection results in an accumulation and a retention of sodium (^99mTc) pertechnetate in the choroid plexus and red blood cells. Intravenous administration of 10-20 µg stannous ion/kg body weight (in form of stannous pyrophosphate) followed 30 minutes later by 370-740 MBq pertechnetate injection results in efficient labelling of blood pool. Under normal circumstances intravenously injected pertechnetate freely diffuses into and out from the erythrocytes. However, when the erythrocytes have been preloaded with stannous ion, the sodium (^99mTc) pertechnetate is reduced within the cells and becomes bound to the chains of globin. The mechanisms by which sodium (^99mTc) pertechnetate becomes attached to tin primed red blood cells are not clearly understood. However, 20% of injected pertechnetate enters the red cell and binds to a beta chain of globin. While the remaining 70-80% of pertechnetate is believed to be located in the cytoplasm or on the red cell membrane. On the other hand reducing the surface charge of the erythrocytes decreases the efficiency of labelling down to 20%.

Organ uptake

The most beneficial time for the injection of (^99mTc) pertechnetate for the in-vivo labelling is 20-30 min after the administration of pyrophosphate. At 10 and 100 minutes post injection, 77 ± 15% and 71 ± 14% respectively, of the injected activity is found in the blood. This value remains constant for about 2 hours after injection with only about 6% decrease in total blood radioactivity during this period.

Up to eight days after the examination, labelling of erythrocytes with (^99mTc) pertechnetate may still be observed. There is no appreciable effect with doses of up to 0.02 mg of tin/kg. The heat-denatured erythrocytes are sequestrated by splenic pulp.

There are no preclinical safety data specific to technetium labelled erythrocytes. The toxicity of pertechnetate ion and stannous salts has been studied and reported in the literature. Systemic toxical effects are only observed at relatively high parenteral doses, giving a safety ratio of at least 150.

Repeated dose toxicity studies in rats with 50-100 times human dose do not cause macroscopic or microscopic alterations. Stannous salts are reported to have a weak potential for mutagenicity. There are no studies describing possible effects on reproduction or tumour incidence.