ArticleCancers2021
Is Hypoxia a Factor Influencing PSMA-Directed Radioligand Therapy?-An In Silico Study on the Role of Chronic Hypoxia in Prostate Cancer.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Time for action: actinium-225 PSMA-targeted alpha therapy for metastatic prostate cancer - a systematic review and meta-analysis.Theranostics · 2025Pooled it
- A Spatiotemporal Image-Guided Model of Radiopharmaceutical Transport in Heterogeneous Vasculature Prostate Tumor: A Computational Analysis of Key Parameters in Lutetium-177 PSMA Therapy.Annals of biomedical engineering · 2026Article
- Combination therapy strategies in engineeredCell communication and signaling : CCS · 2026Review
- The role of the tumor microenvironment in mediating radiopharmaceutical therapy: bridging nuclear medicine and cancer immunotherapy.Military Medical Research · 2026Review
- A mathematical model for the investigation of combined treatment of radiopharmaceutical therapy and PARP inhibitors.European journal of nuclear medicine and molecular imaging · 2025Article
- Multi-scale computational modeling towards efficacy in radiopharmaceutical therapies while minimizing side effects: Modeling of amino acid infusion.PLoS computational biology · 2025Article
- A Comparative Analysis of Alpha and Beta Therapy in Prostate Cancer Using a 3D Image-Based Spatiotemporal Model.Annals of biomedical engineering · 2025Article
- Impact of cell geometry, cellular uptake region, and tumour morphology onEJNMMI physics · 2024Article
- Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model.NPJ systems biology and applications · 2024Article
- Theranostic digital twins: Concept, framework and roadmap towards personalized radiopharmaceutical therapies.Theranostics · 2024Review
- Localized radiotherapy of solid tumors using radiopharmaceutical loaded implantable system: insights from a mathematical model.Frontiers in oncology · 2024Article
- Deciphering the effects of radiopharmaceutical therapy in the tumor microenvironment of prostate cancer: an in-silico exploration with spatial transcriptomics.Theranostics · 2024Article
- Multi-Scale and Multi-Physics Models of the Transport of Therapeutic/Diagnostic Cancer Agents.Cancers · 2023Article
- Article
- Review
- Prostate Microbiota and Prostate Cancer: A New Trend in Treatment.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). It administrates 225Ac- or 177Lu-labeled ligands for the targeted killing of tumor cells. Differently from X- or γ-ray, for the emitted α or β particles the ionization of the DNA molecule is less dependent on the tissue oxygenation status. Furthermore, the diffusion range of electrons in a tumor is much larger than the volume typically spanned by hypoxic regions. Therefore, hypoxia is less investigated as an influential factor for PSMA-directed RLT, in particular with β emitters. This study proposes an in silico approach to theoretically investigate the influence of tumor hypoxia on the PSMA-directed RLT. Based on mice histology images, the distribution of the radiopharmaceuticals was simulated with an in silico PBPK-based convection-reaction-diffusion model. Three anti-CD31 immunohistochemistry slices were used to simulate the tumor microenvironment. Ten regions of interest with varying hypoxia severity were analyzed. A kernel-based method was developed for dose calculation. The cell survival probability was calculated according to the linear-quadratic model. The statistical analysis performed on all the regions of interest (ROIs) shows more heterogeneous dose distributions obtained with 225Ac compared to 177Lu. The higher homogeneity of 177Lu-PSMA-ligand treatment is due to the larger range covered by the emitted β particles. The dose-to-tissue histogram (DTH) metric shows that in poorly vascularized ROIs only 10% of radiobiological hypoxic tissue receives the target dose using 177Lu-PSMA-ligand treatment. This percentage drops down to 5% using 225Ac. In highly vascularized ROIs, the percentage of hypoxic tissue receiving the target dose increases to more than 85% and 65% for the 177Lu and 225Ac-PSMA-ligands, respectively. The in silico study demonstrated that the reduced vascularization of the tumor strongly influences the dose delivered by PSMA-directed RLT, especially in hypoxic regions and consequently the treatment outcome.
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