Technetium ⁹⁹ᵐTc macrosalb

When administered in usual doses, technetium [^99mTc] macrosalb injection shows no pharmacodynamic effects detectable clinically or/and analytically.

Following intravenous injection of technetium [^99mTc] macrosalb injection, temporary occlusion of pulmonary capillaries and arterioles occurs, which is proportional to the regional pulmonary blood flow at the time.

The principle of perfusion scintigraphy is capillary blockade. After intravenous injection most of the macrosalb aggregates are retained in the arterioles and capillaries of the lung at the time of first passage through the lungs. The diameter of most of the macroaggregates is between 10 and 90 micrometer. Depending on the distribution of particle sizes, roughly every 1,000,000^th capillary (diameter <20 micrometer) and every 1,000^th arteriole (diameter >20 micrometer) is temporarily occluded. The extent of the regional blockade with micro embolisms is thus directly proportional to the regional lung perfusion at the time. Larger particles can lead to occlusion of larger vessels and therefore cause artificial perfusion disturbances. Hemodynamic changes are directly linked to the particle size of the macrosalb aggregates.

The elimination of the macroaggregate particles from the lungs takes place by mechanical fragmentation through the systolic-diastolic pressure pulses within the capillaries and by enzymatic breakdown with subsequent phagocytosis by macrophages of the reticuloendothelial system. In the context of elimination, activity accumulates in the liver and kidneys. Liver accumulation is extremely variable; it increases over time and can become as high as approximately 25%. With regard to elimination from the lungs, great differences exist between individuals. The particles are eliminated from the lungs with a biological half-life of about 7-20 hours. 30-45% of the injected radioactivity is excreted through the urine within 24 hours.

If a right-to-left shunt is present, a proportion of the macroaggregates moves into the general circulation system and becomes trapped there in the capillary bed. If this happens, the formation of a cerebral or renal microembolism is, for example, possible.

Correlation exists between the size of the MAA and their toxic effects.

The pathophysiologic mechanism responsible for toxicity is shown to be the increase of the pulmonary blood pressure. With particulars from 10-50 micrometer in diameter the first pulmonary signs of toxicity in dogs (e.g. tachypnea) appear after injection of 20 to 25 mg per kg of body weight.

A sharp increase of the pulmonary blood pressure is noticed when 20 mg of less than 80 micrometer sized macrosalb particles are injected, where no significant pressure changes are recorded with 40 mg of less than 35 micrometer macrosalb particles. With suspension of macrosalb particles up to 150 micrometer diameter, no blood pressure changes appear below 10 mg/kg, while larger diameter suspensions (up to 300 micrometer) typical blood pressure changes in pulmonary artery appear when the doses exceed 5 mg/kg.

Doses of 20-50 mg/kg cause sudden death from failure. A safety factor of 100 is found after injection in dogs of 14,000 particles of technetium [^99mTc] macrosalb (size: 30-50 micrometer).

The repeated-dose toxicity studies performed in dogs show no detectable variations in the general behaviour of the animals.

No evidence of pathological changes in the main organs has been detected.

There is no evidence in the literature of teratogenic, mutagenic or carcinogenic effect of the unlabelled product.