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Although ^99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available “model” radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates <b>^99mTc-TPP-BBN</b> and <b>^99mTc-AO-BBN</b> (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. <b>^99mTc-TPP-BBN</b> and <b>^99mTc-AO-BBN</b> caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener <b>^99mTc-BBN</b>, leading to an augmented formation of γH2AX foci and micronuclei. <b>^99mTc-TPP-BBN</b> also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of <b>^99mTc-TPP-BBN</b> in the mitochondria and enhanced uptake of <b>^99mTc-AO-BBN</b> in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by ^99mTc. In particular, the results obtained for <b>^99mTc-TPP-BBN</b> reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates.