The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered. •41% of the 225Ac-iPSMA taken up by LNCaP cells reached the nucleus.•225Ac-iPSMA specific and stably accumulates at bone metastasis.•Difference between 225Ac-iPSMA and 177Lu-iPSMA dose rate is of five times.