Investigation of the Effects of Compartments in Physiologically Based Pharmacokinetic (PBPK) Model on AUC Calculation in Alpha Therapy Using 212Pb-DOTAMTATE
Asyifa Khoerunnisa (a), Rohma Novitasari (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:
[212Pb]Pb-DOTAMTATE has a purpose in targeted alpha therapy aimed at somatostatin receptor-expressing tumors. Compartmental modeling, especially PBPK modeling, is crucial for understanding radiopharmaceutical distribution and estimating radiation doses to vital organs like the kidney and spleen. The aim of this study was to assess the effect of each compartment in the PBPK model on the calculation of area under the curve (AUC) during alpha therapy using 212Pb-DOTAMTATE.
Methods:
The 212Pb-DOTAMTATE-PBPK model was evaluated using published biokinetic data from [212Pb]Pb-DOTAMTATE in mice bearing AR42J xenografts. A complex model of 212Pb daughters (212Bi, 208Tl, and 208Pb) was created using SAAM II software. The effect of each compartment was assessed by removing the daughter radionuclides individually and comparing the resulting kidney and spleen AUC with the complex model AUC using relative deviation (RD).
Results:
The highest RD was observed for 212Bi-labeled compartments, with the kidney showing 397% and the spleen 285%. This was followed by 212Bi-free compartments, where the kidney showed 18% and the spleen 15%. Removal of 208Tl and 208Pb showed no significant impact.
Conclusion:
Dose estimates for kidney and spleen were significantly affected by the 212Bi-labeled compartment. The model requires further testing with radionuclides daughter data to be more reliable with the PBPK model.

Keywords: 212Pb, PBPK, compartmental model, AUC

Topic: Medical Physics and Biophysics