Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model

• Published in: NPJ systems biology and applications Vol. 10; no. 1; pp. 39 - 17
• Main Authors: Piranfar, Anahita, Moradi Kashkooli, Farshad, Zhan, Wenbo, Bhandari, Ajay, Saboury, Babak, Rahmim, Arman, Soltani, M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/553/2695; 631/67; 639/705/1042; 639/766/747; Bioinformatics; Biological Transport; Biomedical and Life Sciences; Castration; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Convection; Diffusion; Humans; Internalization; Life Sciences; Ligands; Male; Metastases; Pharmaceuticals; Pharmacokinetics; Prostate cancer; Prostatic Neoplasms - radiotherapy; Protein turnover; Radioisotopes; Radiopharmaceuticals; Reaction mechanisms; Receptor density; Solid tumors; Systems Biology; Tumors
• ISSN: 2056-7189; 2056-7189
• DOI: 10.1038/s41540-024-00362-4

Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA)-targeted radiopharmaceutical therapy is a clinically approved treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Even though common practice reluctantly follows “one size fits all” approach, medical community believes there is significant room for deeper understanding and personalization of radiopharmaceutical therapies. To pursue this aim, we present a 3-dimensional spatiotemporal radiopharmaceutical delivery model based on clinical imaging data to simulate pharmacokinetic of 177 Lu-PSMA within the prostate tumors. The model includes interstitial flow, radiopharmaceutical transport in tissues, receptor cycles, association/dissociation with ligands, synthesis of PSMA receptors, receptor recycling, internalization of radiopharmaceuticals, and degradation of receptors and drugs. The model was studied for a range of values for injection amount (100–1000 nmol), receptor density (10–500 nmol•l –1 ), and recycling rate of receptors (10 –4 to 10 –1  min –1 ). Furthermore, injection type, different convection-diffusion-reaction mechanisms, characteristic time scales, and length scales are discussed. The study found that increasing receptor density, ligand amount, and labeled ligands improved radiopharmaceutical uptake in the tumor. A high receptor recycling rate (0.1 min –1 ) increased radiopharmaceutical concentration by promoting repeated binding to tumor cell receptors. Continuous infusion results in higher radiopharmaceutical concentrations within tumors compared to bolus administration. These insights are crucial for advancing targeted therapy for prostate cancer by understanding the mechanism of radiopharmaceutical distribution in tumors. Furthermore, measures of characteristic length and advection time scale were computed. The presented spatiotemporal tumor transport model can analyze different physiological parameters affecting 177 Lu-PSMA delivery.