Tumor Shape-Specific Brachytherapy Implants by 3D-Printing, Precision Radioactivity Painting, and Biomedical Imaging.

In brachytherapy (BT), or internal radiation therapy, cancer is treated by radioactive implants. For instance, episcleral plaques (EPs) for the treatment of uveal melanoma, are designed according to generic population approximations. However, more personalized implants can enhance treatment precision through better adjustment of dose profiles to the contours of cancerous tissues. An original approach integrating biomedical imaging, 3D printing, radioactivity painting, and biomedical imaging, is developed as a workflow for the development of tumor shape-specific BT implants. First, computer-aided design plans of EP are prepared according to guidelines prescribed by the Collaborative Ocular Melanoma Study protocol. Polyetheretherketone (PEEK), a high-performance polymer suitable for permanent implants, is used to 3D-print plaques and the geometrical accuracy of the printed design is evaluated by imaging. The possibility to modulate the dose distribution in a tridimensional manner is demonstrated by painting the inner surfaces of the EPs with radioactive 103Pd, followed by dose profile measurements. The possibility to modulate dose distributions generated by these 3D-printed plaques through radioactivity painting is therefore confirmed. Ex vivo surgical tests on human eyeballs are performed as an assessment of manipulation ease. Overall, this work provides a solution for the fabrication of tumor-specific radioactive implants requiring higher dose precision.

Recent Advances in Brachytherapy Using Radioactive Nanoparticles: An Alternative to Seed-Based Brachytherapy.

Interstitial brachytherapy (BT) is generally used for the treatment of well-confined solid tumors. One example of this is in the treatment of prostate tumors by permanent placement of radioactive seeds within the prostate gland, where low doses of radiation are delivered for several months. However, successful implementation of this technique is hampered due to several posttreatment adverse effects or symptoms and operational and logistical complications associated with it. Recently, with the advancements in nanotechnology, radioactive nanoparticles (radio-NPs) functionalized with tumor-specific biomolecules, injected intratumorally, have been reported as an alternative to seed-based BT. Successful treatment of solid tumors using radio-NPs has been reported in several preclinical studies, on both mice and canine models. In this article, we review the recent advancements in the synthesis and use of radio-NPs as a substitute to seed-based BT. Here, we discuss the limitations of current seed-based BT and advantages of radio-NPs for BT applications. Recent progress on the types of radio-NPs, their features, synthesis methods, and delivery techniques are discussed. The last part of the review focuses on the currently used dosimetry protocols and studies on the dosimetry of nanobrachytherapy applications using radio-NPs. The current challenges and future research directions on the role of radio-NPs in BT treatments are also discussed.

In silico dosimetry of low-dose rate brachytherapy using radioactive nanoparticles.

PURPOSE: Nanoparticles (NPs) with radioactive atoms incorporated within the structure of the NP or bound to its surface, functionalized with biomolecules are reported as an alternative to low-dose-rate seed-based brachytherapy. In this study, authors report a mathematical dosimetric study on low-dose rate brachytherapy using radioactive NPs. METHOD: Single-cell dosimetry was performed by calculating cellular S-values for spherical cell model using Au-198, Pd-103 and Sm-153 NPs. The cell survival and tumor volume versus time curves were calculated and compared to the experimental studies on radiotherapeutic efficiency of radioactive NPs published in the literature. Finally, the radiotherapeutic efficiency of Au-198, Pd-103 and Sm-153 NPs was tested for variable: administered radioactivity, tumor volume and tumor cell type. RESULT: At the cellular level Sm-153 presented the highest S-value, followed by Pd-103 and Au-198. The calculated cell survival and tumor volume curves match very well with the published experimental results. It was found that Au-198 and Sm-153 can effectively treat highly aggressive, large tumor volumes with low radioactivity. CONCLUSION: The accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumor repopulation rate is important for the calculation of cell survival curves. Self-absorption of emitted radiation and dose enhancement due to AuNPs must be considered in the calculations. Selection of radionuclide for radioactive NP must consider size of tumor, repopulation rate and radiosensitivity of tumor cells. Au-198 NPs functionalized with Mangiferin are a suitable choice for treating large, radioresistant and rapidly growing tumors.

Microdosimetric calculations for radionuclides emitting ß and α particles and Auger electrons.

This work focuses on the calculation of S-values and radial energy profiles for radionuclides emitting high (Y-90, Sr-89), medium (Re-186, Sm-153) and low-energy (Er-169, Lu-177) ß-particles, Auger electrons (In-111, Ga-67, I-123) and α-particles (At-211, Ac-225). Simulations were performed using the EGSnrc and GEANT4-DNA Monte Carlo (MC) codes for a spherical cell geometry. S-values were computed using decay spectra available in literature for Tc-99m and In-111. To investigate the effect on S-value when the same emission spectrum is used in two different MC codes. Internal modules of the MC codes were used to simulate the decay of other radionuclides mentioned above. Radial energy profiles for uniformly distributed radioactive sources in the cell nucleus and cytoplasm were calculated and results were compared with the literature. For S-values calculated using the same emission spectrum, the results showed good agreement with each other and with the literature. Whereas, the S-values calculated using the internal decay data of the MC codes, for instance, for Ga-67 and Y-90, showed discrepancies up to 40%. Radial energy profiles were also different from those reported in the literature. Our results show that well validated radiation emission spectra must be used for such calculations and internal decay spectra of MC codes should be used with caution. The normalized probability density functions must be used to sample points uniformly into spherical volumes and the methodology proposed here can be used to correctly determine radial energy profiles.

Comparison of dosimetric accuracy of acuros XB and analytical anisotropic algorithm against Monte Carlo technique.

This study reports the comparison between two dose calculation algorithms, Acuros XB 13.5 (AXB) and Analytical Anisotropic Algorithm (AAA) against Monte Carlo (MC) simulations for 3D-Conformal Radiation Therapy (3D-CRT) using a female pelvic rando phantom. 3D-CRT treatment plans were generated on the CT images of rando phantom using AXB and AAA with Source to Axis Distance (SAD) technique. Doses obtained using two algorithms and MC results were compared using MATLAB based software CERR. In house MATLAB code was developed to calculate the gamma dose distribution comparison in terms of dose difference (DD) and distance to agreement distribution (DTA). The results showed that the Dmean in the PTV TOTAL (PTV) volume for AXB and AAA was equal to the mean dose calculated by MC simulations. The gamma passing rates for AXB were more accurate in comparison to AAA with reference to MC for PTV, Bladder and Femoral Heads region. After analysing the dose comparison specially for the PTV, femoral heads, also the analysis of dose volume histogram (DVH) and gamma dose distribution comparison for PTV, femoral heads and bladder, it can be concluded that AXB is more accurate in comparison to AAA. It can be said that AXB is well suited for dose calculation in clinical setup when compared to MC calculations.

Monte Carlo assessment of low energy electron range in liquid water and dosimetry effects.

The effects of low energy electrons in biological tissues have proved to lead to severe damages at the cellular and sub-cellular level. It is due to an increase in the relative biological effectiveness (RBE) of these electrons with a decrease in their penetration range. That is, lower the range higher will be its RBE.Therefore, accurate determination of low energy electron range becomes a key issue for radiation dosimetry. This work reports on in-water electron tracks evaluated at low kinetic energy (1-50 keV) using isotropic mono-energetic point source approach suitably implemented by different general-purpose Monte Carlo codes. For this aim, simulations were performed using PENELOPE, EGSnrc, MCNP6, FLUKA and Geant4-DNA Monte Carlo codes to obtain the particle range, R,R90,R50. Finally, evaluation of dose point kernel (DPK), as used for internal dosimetry, was carried out as an application example. Scaled dose point kernels (sDPK) were estimated for a range of mono-energetic low energy electron sources. The non-negligible differences among the calculated sDPK using different codes were obtained for energy electrons up to 5 keV. It was also observed that differences of in-water range for low-energy electrons, due to the different general-purpose Monte Carlo codes, affected the DPKs used for dosimetry by convolution approach. Finally, the 3D dosimetry was found to be almost not affected at macroscopic clinical scale, whereas non-negligible differences appeared at the microscopic level. Hence, a thorough validation of the used sDPKs have to be performed before they could be used in applications to derive any conclusions.