Dosimetric calculation of ¹⁷⁷Lu-iPSMA and ²²⁵Ac-iPSMA at cellular level in a bone metastasis model

Bone metastases derived from prostate cancer generate a large number of adverse symptoms, and can be treated with third-generation radiopharmaceuticals, allowing a longer life expectancy. Radiopharmaceuticals such as ¹⁷⁷Lu-iPSMA or ²²³RaCl₂ have been used to treat these metastases, obtaining a poor complete remission or producing toxicity in healthy tissues. In the present work, the absorbed dose due to a new radiopharmaceutical, ²²⁵Ac-iPSMA, has been compared with ¹⁷⁷Lu-iPSMA, in bone metastases produced in a murine model. The absorbed dose was determined based on the Medical Internal Radiation Dose (MIRD) methodology. The absorbed dose was obtained as the product of the accumulated activity in an organ and the corresponding dose factor. Dose factors were obtained for both radiopharmaceuticals by Monte Carlo simulations, using the MCNPX 5 code. Cumulative activity was determined in the nucleus of tumor cells, previously generated in male CD1 mice using an intra-femur-tibial LNCaP cell inoculation model, as well as in some risk organs such as lungs, kidneys, liver, intestine, spleen and skeleton. This was achieved by evaluating the biodistribution of both radiopharmaceuticals at five different times, and whose data were entered in the OLINDA software to obtain the biokinetic models of both. Using these models it was possible to determine the accumulated activity due to both radiopharmaceuticals, with these the absorbed dose in the nucleus of metastatic prostate cancer cells was determined and this value was compared for both radiopharmaceuticals. It was obtained that for the tumor the dose ratio between ²²⁵Ac-iPSMA and ¹⁷⁷Lu-iPSMA was approximately 5, being 2.3 Gy for the first and 0.5 Gy for the second, both per unit of MBq injected. (author)