Radiopharmaceuticals (RPs) specific to prostate-specific membrane antigen (PSMA) are extremely promising for radioligand therapy of prostate cancer. The aim of this work was to study the general toxic properties of radiopharmaceutical 225Ac-DOTA-PSMA after its single intravenous administration to laboratory animals (“acute” toxicity). It was shown that the administration of 225Ac-DOTA-PSMA to mice and rats (males and females) in doses of 100, 200, and 500 kBq/kg was satisfactorily tolerated by the animals. No significant signs of intoxication or death of animals were observed. No pathomorphological changes in internal organs and tissues were detected at autopsy of animals. In mice treated with 225Ac-DOTA-PSMA at doses of 200 and 500 kBq/kg, a decrease in the mass of salivary glands by 8–15% was observed compared to the control group (p > 0.05).