scholarly journals Is Hypoxia a Factor Influencing PSMA-Directed Radioligand Therapy?—An In Silico Study on the Role of Chronic Hypoxia in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3429
Author(s):  
Gabriele Birindelli ◽  
Milos Drobnjakovic ◽  
Volker Morath ◽  
Katja Steiger ◽  
Calogero D’Alessandria ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
Regions Of Interest ◽  
Influential Factor ◽  
Quadratic Model ◽  
Target Dose ◽  
Radioligand Therapy ◽  
Psma Ligand ◽  
Reaction Diffusion Model ◽  
In Silico Study

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.

Trans-rectal thermo-acoustic computed tomography: An initial in silico study

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Sovanlal Mukherjee ◽  
Charles Bunting ◽  
Daqing Piao
Keyword(s):  
Prostate Cancer ◽  
Computed Tomography ◽  
Cancer Detection ◽  
In Silico ◽  
Power Loss ◽  
Acoustic Pressure ◽  
Conductivity Distribution ◽  
Imaging Geometry ◽  
Prostate Cancer Detection ◽  
In Silico Study

AbstractBackground: The purpose of this in silico study is to demonstrate thermo-acoustic computed tomography (CT) based reconstruction of frequency-dependent true electrical conductivity distribution in a trans-rectal axialimaging geometry. Since cancerous tissue is expected to exhibit different conductivity profile compared to normal tissue, reconstructing conductivity based on thermoacoustic CT in a trans-rectal geometry has a potential for prostate cancer detection.Methodology: A trans-rectal axial-imaging geometry is illuminated by an electromagnetic (EM) point source at a microwave frequency. The source is located on a transrectal EM applicator close to the rectal wall. The applicator also houses a convex-array of point acoustic receivers that capture the acoustic pressure generated within the geometry as a result of EM illumination. The finite element method (FEM) along with an absorbing boundary condition is applied for solving the electric field (E-field) distribution, the power loss density and the acoustic pressure. The Levenberg-Marquardt regularization scheme is applied to reconstruct the conductivity distribution by decoupling the E-field from the power loss density.Results: For an excitation frequency of 915 MHz, various 2-D reconstructed images based on a 2:1 conductivity ratio between the background and object in a trans-rectal geometry of 40 mm radius are shown. Both single and double objects of 3 mm radius positioned at 4, 7, 10 and 15 mm depth with respect to the acoustic receiver are considered. The quality of the reconstructed image is shown to be object-depth dependent. The effect of different levels of Gaussian noise on the reconstructed images is shown. The contrast-to-noise ratios (CNRs) of the reconstructed images for the objects of different sizes and depths are also computed.Conclusions: Feasibility of recovering heterogeneous conductivity distribution in a trans-rectal axial-imaging geometry by thermo-acoustic CT is demonstrated in silico. The results implicate an alternative imaging mechanism for prostate cancer detection.

scholarly journals Prostate-specific membrane antigen (PSMA)–ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer

2020 ◽  
Vol 50 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Ukihide Tateishi
Keyword(s):  
Prostate Cancer ◽  
Emission Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Clinical Perspective ◽  
Radioligand Therapy ◽  
Psma Ligand ◽  
Interpretation Criteria ◽  
Positron Emission ◽  
Previous Decade ◽  
Specific Membrane

Abstract From a clinical perspective, prostate-specific membrane antigen (PSMA) is a valuable target for both diagnosis and radioligand therapy (RLT) of prostate cancer. The term ‘specific’ has been used to characterize a histologic hallmark of overexpression in the membrane of most prostate cancer. Many PSMA ligands have been developed since the previous decade and have been used in several clinical trials and clinical studies. However, procedure, specification, protocol, interpretation criteria, radiation dose, and cost-effectiveness of PSMA ligands have not been fully explained. Regardless of worldwide use of promising PSMA-ligand PET and RLT, it has not been approved in Japan. Expedited introduction of PSMA-ligand PET and RLT to Japan and implementation of clinical study are eager for many patients with prostate cancer.

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