Multi-scale computational modeling towards efficacy in radiopharmaceutical therapies while minimizing side effects: Modeling of amino acid infusion
Fig 2
Multi‑Compartment PBPK model and spatial simulation domain for radiopharmaceutical transport in tumor tissue.
(A) Solution domain and microvascular network distribution and Schematic of the Multi-Compartment Model for tumor in radiopharmaceutical therapy. This diagram represents a multi-compartmental physiologically based pharmacokinetic model detailing the distribution and interaction radiopharmaceuticals within four distinct physiological spaces: vascular, interstitial, cell membrane, and intracellular compartments. The transient mass transfer simulation incorporates convective contributions and applies the multi-compartment model to track solute dynamics across the biophysical domains. Key Steps: 1: Physical decay of radionuclide; 2 & 3 Exchange of radiopharmaceuticals between the vascular and interstitial compartments; 4 & 5: Binding and subsequent unbinding of the free drug to receptors on cell membrane; 6: Internalization of peptides that bound to receptors into intracellular space; 7: clearance of radiopharmaceuticals. Image created using Servier Medical Art (https://smart.servier.com/), licensed under CC BY 4.0. (B) Illustration of Solution Domain with Microvascular Network Distribution and Boundary Conditions. The simulation focuses on a tumor with an approximate diameter of 16 mm, embedded in a domain that also includes adjacent normal tissue. The microvascular network comprises vessels with diameters around 20 μm, branching from larger parent vessels of about 400 μm in diameter [118]. Vascular architecture is generated based on the sprouting angiogenesis model originally formulated by Anderson and Chaplain [57,58], with vessel density increasing in response to local concentrations of tumor angiogenic factors. This leads to a complex capillary network with enhanced branching and loop formation in the tumor region. The domain extends 2 mm beyond the tumor margin to capture the full therapeutic range of 177Lu, with emphasis placed on modeling both intratumoral and peritumoral transport phenomena.