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[225Ac]Ac-DOTA-TDA is a targeted alpha therapy radiopharmaceutical consisting of actinium-225 (a potent alpha-particle-emitting radionuclide) chelated to DOTA-TDA, a derivative combining the DOTA chelator and tetradecylamine (TDA)[1][4]. It is designed for transarterial radioembolization (TARE), particularly for targeted therapy of primary and secondary liver tumors, including hepatocellular carcinoma (HCC) and colorectal cancer liver metastases[1][2][4]. The compound is highly stable in serum and demonstrates high radiochemical purity. Upon intra-arterial administration, it selectively accumulates in hepatic tumors due to the preferential arterial blood supply of tumor tissue. Its cytotoxic effect is mediated through the emission of high linear energy transfer alpha particles from actinium-225, causing lethal DNA damage in targeted tumor cells with sparing of surrounding normal tissue due to the short path length of alpha radiation[1][2]. Studies in animal models have shown improved survival compared to controls and promise for further clinical development in treating hepatic tumors[1][2]. The agent is often formulated in Lipiodol for intra-arterial delivery[1][2].
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