Impact of Varying the Maximum Tolerated Dose for Kidney on the Predicted Distribution of Ac-225-mcp-M-alb-PSMA and Its Daughters in Alpha Therapy
Rosa Desinta (a), Jenni Natalia Corebima (a), Assyifa Rahman Hakim (a), Deni Hardiansyah (a*)

a) Medical Physics and Biophysics, Physics Department, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, Indonesia
*denihardiansyah[at]ui.ac.id

Abstract

Background:
Actinium-225 is offering high cytotoxicity and therapeutic efficacy for prostate cancer. Accurate prediction of radiopharmaceutical biodistribution, organ dosimetry, and potential toxicity can be achieved through physiologically based pharmacokinetic (PBPK) modeling. This study aims to assess the impact of varying maximum tolerated renal doses on the predicted distribution of Ac-225-mcp-M-alb-PSMA and its daughters (Fr-221, Bi-213, Po-213, Pb-209, and Tl-209).
Methods:
A PBPK model adapted from Zaid et al. was evaluated using published biokinetic data from LNCaP tumor-bearing SCID mice. Simulations applied human physiological parameters with maximum renal absorbed doses ranging from 1 to 6 Gy per cycle. The area under the curve (AUC) for Ac-225 and its daughters was obtained from SAAM II for each compartment and analyzed relative to the 6 Gy reference dose.
Results:
The relative deviation (RD) of the AUC for Ac-225 and its daughters in each compartment was 83%, 67%, 50%, 33%, and 16% at doses of 1-5 Gy compared to 6 Gy. These RDs decreased with increasing dose.
Conclusion:
Variations in kidney dose influence AUC distribution. While daughter radionuclide toxicity may be inferred from parent data, further validation of PBPK model structures is needed to confirm these findings.

Keywords: PBPK model, AUC, Ac-225

Topic: Medical Physics and Biophysics