Abstract
In vivo alpha particle generators have great potential for the treatment of neuroendocrine tumors in alpha-emitter-based peptide receptor radionuclide therapy (α-PRRT). Quantitative pharmacokinetic analyses of the in vivo alpha particle generator and its radioactive decay products are required to address concerns about the efficacy and safety of α-PRRT. A murine whole-body physiologically based pharmacokinetic (PBPK) model was developed for212Pb-labeled somatostatin analogs (212Pb-SSTA). The model describes pharmacokinetics of212Pb-SSTA and its decay products, including specific and non-specific glomerular and tubular uptake. Absorbed dose coefficients (ADC) were calculated for bound and unbound radiolabeled SSTA and its decay products. Kidneys received the highest ADC (134 Gy/MBq) among non-target tissues. The alpha-emitting212Po contributes more than 50% to absorbed doses in most tissues. Using this model, it is demonstrated that α-PRRT based on212Pb-SSTA results in lower absorbed doses in non-target tissue than α-PRRT based on212Bi-SSTA for a given kidneys absorbed dose. In both approaches, the energies released in the glomeruli and proximal tubules account for 54% and 46%, respectively, of the total energy absorbed in kidneys. The212Pb-SSTA-PBPK model accelerates the translation from bench to bedside by enabling better experimental design and by improving the understanding of the underlying mechanisms.
Original language | English |
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Article number | 2132 |
Journal | Pharmaceutics |
Volume | 13 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2021 |
Keywords
- In vivo alpha particle generators
- Murine PBPK model
- Neuroendocrine tumors
- [Pb]Pb-DOTAMTATE
- α-PRRT