Study the Effect of Compartments in Physiologically Based Pharmacokinetic (PBPK) model of Alpha Therapy Using Ac-225 mcp-M-alb-PSMA to the AUC calculation Jenni Natalia Corebima (a), Rosa Desinta (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:
[Ac-225]Ac-mcp-M-alb-PSMA is used in targeted alpha therapy for prostate cancer. Compartmental modeling is essential to understand radiopharmaceutical distribution and identify high-risk organs. The kidneys, being critical organs susceptible to toxicity, require precise dose estimation. This study aims to evaluate the effect of each compartment in PBPK model on the AUC calculation for alpha therapy using [Ac-225]Ac-mcp-M-alb-PSMA.
Methods:
Ex vivo biodistribution data for kidney uptake were obtained from 8-week-old LNCaP tumor-bearing SCID mice. PBPK modeling was performed using SAAM II software to estimate the area under the curve (AUC). The reference AUC (rAUC) was calculated based on a complete compartmental model structure of [225Ac]Ac-mcp-M-alb-PSMA. This rAUC was compared to the AUC estimates obtained after removal of each Ac-225 daughter (Fr-221, Bi-213, Po-213, Pb-209, and Tl-209) from the model. The effect was evaluated by comparing each modified AUC estimate to the rAUC using relative deviation (RD).
Results:
Removal of Fr-221-labeled pharmaceuticals showed the highest deviation in kidney AUC estimation, with an RD of 147%, followed by Fr-221-free (11%). Excluding other daughters showed a small effect on the calculated AUC.
Conclusion:
Fr-221-labeled pharmaceuticals significantly affected the AUC in the kidney. However, further validation with daughter radionuclide biokinetic data is needed to improve the reliability of the PBPK analysis.
