High Atomic Number Nanoparticles Research Articles

Comparison of MCNPX and EGSnrc Monte Carlo Codes in the Calculation of Nano-Scaled Absorbed Doses and Secondary Electron Spectra around Clinically Relevant Nanoparticles

Purpose: Absorbed dose enhancement due to the presence of high atomic number Nanoparticles (NP)s has been estimated and modeled by Monte Carlo (MC) simulation methods. In the current study, two MC codes of Monte Carlo N‐Particle eXtended (MCNPX) and EGSnrc codes were compared by calculation of secondary electron energy spectra and nano-scaled dose values around four types of spherical NPs.
 Materials and Methods: The MC model was composed of a spherical nanoparticle with a diameter of 50 nm and mono-energetic sources of photons with energies of 30,60, and 100 keV. The secondary electrons emitted from the nanoparticle were scored on the nanoparticle surface and the delivered dose to water around the nanoparticle was tallied using concentric shells with a thickness of 25 nm. Four different elements were used as materials of NPs, including Gold, Bismuth, Gadolinium, and Hafnium.
 Results: Our results showed a considerable difference in the number of emitted electrons per incident photon between the two codes. There were also discrepancies between the two codes in the energy spectra of secondary electrons. Calculated radial dose values around NPs in nano-scale had a similar pattern for both codes. However, significant differences existed for some elements.
 Conclusion: It can be concluded that the results of nano-scaled MC modeling for nanoparticle-based radiation therapy are dependent on the code type and its algorithm for electron transport as well as exploited cross-section libraries.

Metallic nanoparticles for CT-guided imaging of tumors and their therapeutic applications

Nanoparticles (NPs) serve as the contrasting agent in the computed tomography (CT) guided interventional devices and processes. The high contrast imaging of the patient is critical for accurate and early diagnosis, and thereafter the elimination of the abnormality. A high contrast CT scan helps in the diagnosis of blood clots, broken bones, carcinogenic tumors, infections, internal injuries and bleeding, and cardiovascular diseases. Thereafter it helps in the determination of the precise location of surgery, biopsy, and monitoring conditions after surgery. Besides iodine, today radiologists are interested in high atomic number NPs like gold, tantalum, bismuth, silver, etc. The advancement in NP-based CT-guided imaging for a specific target is highly desirable for effective intervention processes like drainage by catheter, needle insertion, etc. In computed tomography (CT) guided interventional devices and procedures, NPs are known to act as contrasting agents. High-contrast imaging of the patient is essential for an accurate and prompt diagnosis, followed by the treatment of the diseased site. Blood clots, shattered bones, cancerous tumors, infections, internal injuries and bleeding, and cardiovascular disorders can be easily diagnosed with the use of a CT scan with high contrast. In addition, it aids in determining the precise surgical site, conducting biopsies, and monitoring postoperative conditions. Iodine-based contrast agents have been the conventional choice, but lately, radiologists are also interested in NPs with a high atomic number, such as gold, tantalum, bismuth, silver, etc. This review talks about recent research on metallic NPs and the usage of their conjugates for CT imaging of tumors, special attention has been given to gold NPs.

Iodine Nanoparticles (Niodx™) for Radiotherapy Enhancement of Glioblastoma and Other Cancers: An NCI Nanotechnology Characterization Laboratory Study.

Effective and durable treatment of glioblastoma is an urgent unmet medical need. In this article, we summarize a novel approach of a physical method that enhances the effectiveness of radiotherapy. High atomic number nanoparticles that target brain tumors are intravenously administered. Upon irradiation, the nanoparticles absorb X-rays creating free radicals, increasing the tumor dose several fold. Radiotherapy of mice with orthotopic human gliomas and human triple negative breast cancers growing in the brain showed significant life extensions when the nanoparticles were included. An extensive study of the properties of the iodine-containing nanoparticle (Niodx) by the Nanotechnology Characterization Laboratory, including sterility, physicochemical characterization, in vitro cytotoxicity, in vivo immunological characterization, and in vivo toxicology, is presented. In summary, the iodine nanoparticle Niodx appears safe and effective for translational studies toward human use.

Microdosimetric Investigation and a Novel Model of Radiosensitization in the Presence of Metallic Nanoparticles.

Auger cascades generated in high atomic number nanoparticles (NPs) following ionization were considered a potential mechanism for NP radiosensitization. In this work, we investigated the microdosimetric consequences of the Auger cascades using the theory of dual radiation action (TDRA), and we propose the novel Bomb model as a general framework for describing NP-related radiosensitization. When triggered by an ionization event, the Bomb model considers the NPs that are close to a radiation sensitive cellular target, generates dense secondary electrons and kills the cells according to a probability distribution, acting like a “bomb.” TDRA plus a distance model were used as the theoretical basis for calculating the change in α of the linear-quadratic survival model and the relative biological effectiveness (RBE). We calculated these quantities for SQ20B and Hela human cancer cells under 250 kVp X-ray irradiation with the presence of gadolinium-based NPs (AGuIXTM), and 220 kVp X-ray irradiation with the presence of 50 nm gold NPs (AuNPs), respectively, and compared with existing experimental data. Geant4-based Monte Carlo (MC) simulations were used to (1) generate the electron spectrum and the phase space data of photons entering the NPs and (2) calculate the proximity functions and other related parameters for the TDRA and the Bomb model. The Auger cascade electrons had a greater proximity function than photoelectric and Compton electrons in water by up to 30%, but the resulting increases in α were smaller than those derived from experimental data. The calculated RBEs cannot explain the experimental findings. The relative increase in α predicted by TDRA was lower than the experimental result by a factor of at least 45 for SQ20B cells with AGuIX under 250 kVp X-ray irradiation, and at least four for Hela cells with AuNPs under 220 kVp X-ray irradiation. The application of the Bomb model to Hela cells with AuNPs under 220 kVp X-ray irradiation indicated that a single ionization event for NPs caused by higher energy photons has a higher probability of killing a cell. NPs that are closer to the cell nucleus are more effective for radiosensitization. Microdosimetric calculations of the RBE for cell death of the Auger electron cascade cannot explain the experimentally observed radiosensitization by AGuIX or AuNP, while the proposed Bomb model is a potential candidate for describing NP-related radiosensitization at low NP concentrations.

A Monte Carlo Study on Dose Enhancement in the Presence of Nanoparticles by Photon Source: A Comparison between Various Concentration and Material of Nanoparticles

Purpose: Recently, the application of high atomic number nanoparticles is suggested in the field of radiotherapy to improve physical dose enhancement and hence treatment efficiency. Several factors such as concentration and material of nanoparticles and energy of beam define the amount of dose enhancement in the target in the presence of nanoparticles.
 Materials and Methods: In this approach, a spherical cell was simulated through the Geant4 Monte Carlo toolkit which contained a nucleus and nanoparticles distributed through the cell. To investigate the effect of the concentration of nanoparticles on the deposited dose, it ranged from 3 mg/g to 30 mg/g for different materials like gold, silver, gadolinium, and platinum. Also, various mono-energetic photon beams included low and high energy sources were applied.
 Results: The results proved that as the concentration increased, the Dose Enhancement Factor (DEF) enlarged. Overall, almost for all energy and material that were used in this study, the maximum of DEF values occurred in the concentration of 30 mg/g. Moreover, lower energy sources presented higher DEF compared to other sources. The results indicated that the highest amount of DEF transpired for 35 keV photon beams equal to 14.67. Also, the K-edge energy of each material affects DEF values.
 Conclusion: To obtain a better outcome in the use of nanoparticles in combination with radiotherapy, a higher concentration of nanoparticles and low-energy photons should be considered to optimize the DEF and thus the treatment ratio.

Abstract 1389: Bismuth gadolinium nanoparticles enhance radiation therapy in hepatocellular carcinoma

Abstract Introduction: Primary cancers of the liver is the fourth most common cause of cancer-related deaths and the second most lethal tumor, with a 5-year survival rate of only 18%. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although HCC is a radiosensitive tumor, radiotherapy (RT) has had a limited role in therapy due to the sensitivity of normal liver parenchyma, thus minimizing radiation exposure is optimal. High atomic number nanoparticles (NP) like bismuth (Bi) and gadolinium (Gd) have been shown to be effective radiosensitizers. Exposure of NP to ionizing radiation leads to the emission of secondary electrons and photons that can damage cells by free radical components, resulting in radiation dose-enhancement. Here we synthesized a multifunctional theranostic NP containing both Bi and Gd (BiGdNP) that can act both as a radiosensitizer and as a bimodal contrast agent for T1 MRI and CT imaging. Materials and Methods: BiGdNP were synthesized using one-pot thermal decomposition of Bi(III) acetate and Gd(III) acetate. Morphology of the NP was characterized by transmission electron microscopy (TEM, JEOL) while Bi and Gd were quantified by inductively coupled plasma-mass spectrometry (ICP-MS, Agilent). Dose-dependent cytotoxicity of BiGdNP was assessed by alamarBlueTM assay. HepG2 cells with BiGdNP were irradiated at 0, 2, and 4 Gy using a 137Cs irradiator. Irradiated cells were incubated at 300 cells/well for 2 weeks. Surviving colonies (1 colony ≥50 cells) were fixed with 10% formalin and stained with 0.5% crystal violet for counting. Magnetic resonance imaging at 4.7 Tesla (Bruker) and micro-computed tomography imaging (GE Medical Systems) were performed on BiGdNP-injected C57BL/6 mice to evaluate liver uptake. Results: Synthesized BiGdNP have good size and shape uniformity with average size of 118 ± 16 nm. No significant difference in cell viability was observed with non-treated and BiGdNP-treated cells at a maximum concentration of 50 μg/mL (p>0.05, t test). This concentration was then used to treat the cells prior to gamma irradiation. In the absence of RT, no adverse effects were observed with BiGdNP-treated cells. For both the 2 and 4 Gy doses, surviving fractions in the BiGdNP-treated groups were decreased than non-treated groups (p<0.05, t test). In addition to radiosensitization, increasing the BiGdNP concentration resulted in increased radiopacity in μ- CT and shorter T1 relaxation time in MRI in vitro and contrast enhancement of the liver in both μ-CT and MRI following intravenous administration in vivo. Conclusion: BiGdNP in combination with RT is more efficient in reducing reproductive viability of HCC than RT alone. The added MRI/CT imaging modality can potentially aid in the visualization of tumor delineation to facilitate localized radiation treatment. Citation Format: Avinash Kakulavar, Raniv D. Rojo, Jossana A. Damasco, Marites P. Melancon, Joy V. Perez. Bismuth gadolinium nanoparticles enhance radiation therapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1389.

Estimation of Dose Enhancement for Inhomogeneous Distribution of Nanoparticles: A Monte Carlo Study

High atomic number nanoparticles are of increasing interest in radiotherapy due to their significant positive impact on the local dose applied to the treatment site. In this work, three types of metal nanoparticles were utilized to investigate their dose enhancement based on the GATE Monte Carlo simulation tool. Gold, gadolinium, and silver were implanted at three different concentrations to a 1 cm radius sphere to mimic a cancerous tumor inside a 10 × 10 × 30 cm3 water phantom. The innermost layer of the tumor represents a necrotic region, where the metal nanoparticles uptake is assumed to be zero, arising from hypoxic conditions. The nanoparticles were defined using the mixture technique, where nanoparticles are added to the chemical composition of the tumor. A directional 2 × 2 cm2 monoenergetic photon beam was used with several energies ranging from 50 keV to 4000 keV. The dose enhancement factor (DEF) was measured for all three metal nanoparticles under all beam energies. The maximum DEF was ~7 for silver nanoparticles with the 50 keV beam energy at the highest nanoparticle concentration of 30 mg/g of water. Gold followed the same trend as it registered the highest DEF at the 50 keV beam energy with the highest concentration of nanoparticles at 30 mg/g, while gadolinium registered the highest at 100 keV.

Dosimetric effect of nanoparticles in the breast cancer treatment using INTRABEAM® system with spherical applicators in the presence of tissue heterogeneities: A Monte Carlo study

Using the 50 kV INTRABEAM® IORT system after breast-conserving surgery: tumor recurrence and organs at risk (OARs), such as the lung and heart, long-term complications remain the challenging problems for breast cancer patients. So, the objective of this study was to address these two problems with the help of high atomic number nanoparticles (NPs). A Monte Carlo (MC) Simulation type EGSnrc C++ class library (egspp) with its Easy particle propagation (Epp) user code was used. The simulation was validated against the measured depth dose data found in our previous study (Tegaw, et al 2020 Dosimetric characteristics of the INTRABEAM ® system with spherical applicators in the presence of air gaps and tissue heterogeneities, Radiat. Environ. Biophys. (10.1007/s00411-020-00835-0)) using the gamma index and passed 2%/2 mm acceptance criteria in the gamma analysis. Gold (Au) NPs were selected after comparing Dose Enhancement Ratios (DERs) of bismuth (Bi), Au, and platinum (Pt) NPs which were calculated from the simulated results. As a result, 0.02, 0.2, 2, 10, and 20 mg-Au/g-breast tissue were used throughout this study. These particles were not distributed in discrete but in a uniform concentration. For 20 mg-Au/g-breast tissue, the DERs were 3.6, 0.420, and 0.323 for breast tissue, lung, heart, respectively, using the 1.5 cm-diameter applicator (AP) and 3.61, 0.428, and 0.335 forbreast tissue, lung, and heart using the 5 cm-diameter applicator, respectively. DER increased with the decrease in the depth of tissues and increase in the effective atomic number (Zeff) and concentration of Au NPs, however, there was no significant change as AP sizes increased. Therefore, Au NPs showed dual advantages such as dose enhancement within the tumor bed and reduction in the OARs (heart and lung).

Dosimetry of tumor targeting imaging by convergent X-ray beam as compared with nuclear medicine

During decades nuclear medicine procedures, based on radiolabeled agents, have proved to be efficient for diseases diagnosis and treatment. Radiation emerging from patient is detected aimed at localizing radiotracer distribution that is further correlated with biochemical/metabolic physiological processes. However, a significant drawback associated with current nuclear medicine procedures implementing radionuclide infusion regards to the inherent absorbed dose as well as radiopharmaceuticals' production, storage and elimination from patient body, thus representing a risk at patient and public health level.In the recent years, alternative methods have been proposed to reduce/eliminate radionuclides in some nuclear medicine procedures. The combination of high atomic number nanoparticles infused within patient body with incident X-ray beam, like tumor targeting and treatment, appears as a potential alternative method capable of theranostics. The process is based on inducing X-ray fluorescence and secondary electrons emission in high atomic number nanoparticles by means of excitation with an external X-ray beam, avoiding employing radioactive substances.The present work reports on the dosimetry performance of both methods, comparing whenever the external convergent X-ray beam alternative may involve less or larger radiation dose levels, according to comparable signal/image quality during the procedure. To this aim, a simplified theoretical model is proposed and associated Monte Carlo simulations are performed in order to compare typical case of nuclear medicine imaging with potential performance of an innovative method, called OXIRIS (Orthovoltage X-ray Induced Radiation and Integrated System), based on convergent X-ray beam exciting high atomic number nanoparticles infused in patient.The obtained results support the proposed alternative method's feasibility, once demonstrated that patient absorbed dose levels are relative similar to those currently used by nuclear medicine procedures, whereas dose to targeted region (tumor) are significantly higher, which may be useful for treatment purposes.

Main Approaches to Enhance Radiosensitization in Cancer Cells by Nanoparticles: A Systematic Review

In recent years, high atomic number nanoparticles (NPs) have emerged as promising radio-enhancer agents for cancer radiation therapy due to their unique properties. Multi-disciplinary studies have demonstrated the potential of NPs-based radio-sensitizers to improve cancer therapy and tumor control at cellular and molecular levels. However, studies have shown that the dose enhancement effect of the NPs depends on the beam energy, NPs type, NPs size, NPs concentration, cell lines, and NPs delivery system. It has been believed that radiation dose enhancement of NPs is due to the three main mechanisms, but the results of some simulation studies failed to comply well with the experimental findings. Thus, this study aimed to quantitatively evaluate the physical, chemical, and biological factors of the NPs. An organized search of PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed. In total, 77 articles were thoroughly reviewed and analyzed. The studies investigated 44 different cell lines through 70 in-vitro and 4 in-vivo studies. A total of 32 different types of single or core-shell NPs in different sizes and concentrations have been used in the studies.

Dosimetric evaluation of gold nanoparticle aided intraoperative radiotherapy with the Intrabeam system using Monte Carlo simulations

Radiosensitization using high atomic number nanoparticles (NPs) has been shown to be an effective method to enhance radiotherapy efficiency. The pathways by which NPs cause sensitization, are generally categorized as physical, chemical and biological effects. Specifically in the case of keV photon radiotherapy where the contribution of physical effects in radiosensitization mechanism is considerable, Monte Carlo (MC) simulations have been an efficient tool to predict the radioenhancement level and to calculate dose enhancement factor (DEF). To-date, several analytical, simulational and experimental studies have reported the radiosensitization effect of gold nanoparticles (GNPs) in various brachytherapy situations. In this work we report for the first time, the DEFs achievable in intraoperative radiotherapy through use of the Intrabeam system and its spherical applicators with addition of GNPs. The MCNPX Monte Carlo code was used for radiation transport and dose calculations. The results of macroscopic and microscopic analysis show that for the Intrabeam system and a homogeneous distribution of 50 nm diameter GNPs, respective DEFs of up to some 1.5, 2, 2.5 and 3 in the tumour bed can be achieved with 5, 10, 15 and 20 mg/g concentrations. Due to rapid change in electron spectra, DEFs greater than 1 mm separation from the applicator surface decrease with distance, offering an additional advantage.

Synchrotron-Based Infrared Microscopy Studies of the Radiosensitization Effects of Nanoparticles used in Radiotherapy

Radiotherapy (RT) is the most important non-surgical modality for cancer and the recent technological advances brought a substantial gain in the balance between the probability of tumor control and the risk of normal tissue complications. However, the clinical management of some radioresistant tumors (such as brain gliomas) continues being a challenge since tumor doses are constrained by the surrounding healthy tissue tolerances. Within this context, new modalities such as radiosensitization in the presence of high atomic number nanoparticles (NP) are extensively evaluated, with the main goal of enhancing the differential effect between tumors and healthy tissues. In the present work, Synchrotron based Fourier Transform Infrared Microspectroscopy (SR-FTIRM), a vibrational spectroscopic technique for the biochemical cell analysis on a microscopic scale, provides relevant information on the treatment-induced modifications of the main biomolecules (nucleic acids, proteins and lipids). A series of treatments, including various NP sized, typed and chemical natured (3 nm gadolinium (GdNP), 1.9 nm gold (AuNP) nanoparticles), cell line used (F98 murine and U87-MG human glioma cells) and radiotherapy configuration (megavoltage X-ray photon energy (MV) normaly used in clinics, with respect to kilovoltage photons (kV)), were assessed for their induced cell macromolecular damages (Martinez-Rovira et al. (2019) Analyst 144, 5511 and DOI: 10.1039/c9an01109a). Additionally, alongside X-ray photon RT, the possible cell damages caused by several charged particle beams (proton, helium, carbon and oxygen) were also considered. Briefly, the biochemical information provided by the highly brilliant infrared light source produced at ALBA Synchrotron leads to a clear advantage in spectral quality at a cellular level and allow better characterization of NP induced damage in cells.

Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams.

Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams. In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay. Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations. Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy.

IMPACT OF NANOPARTICLE CLUSTERING ON DOSE RADIO-ENHANCEMENT.

High atomic number nanoparticles (NPs) have been shown to enhance the effects of radiation in vitro and in vivo. However, NPs are often observed to cluster together, leading to inhomogeneous distribution within the tissue and within cells themselves. The effect of this clustering on the capability of NPs to enhance radiation dose has not yet been fully investigated. In this Monte Carlo simulation study, the dependence of radio-enhancement on a separation parameter characterising NP clustering was investigated. A target water cube of side length 100 μm was simulated containing gold NPs constituting ~1% by mass. The NPs were placed in a cubic grid pattern and the separation distance between nanoparticles was varied. For NPs of 100 nm radius widely separated 2 μm apart, 91% of the total energy deposit was found to occur in the surrounding water, compared to only 56% when the NPs were moved closer together to 0.2 μm. The remaining energy deposit was absorbed by the NPs themselves. A similar trend was observed for NPs of radius 50 nm. The clustering effect was found to persist to greater separations for the larger NPs. The proportion of energy deposit in the available water of the target impacts the potential for cellular damage. Energy deposited within nanoparticles is unlikely to cause biological damage, as ionisations in the surrounding water are required to create radical oxygen species which then progress to cause the biological response to radiation. Clustering of nanoparticles is therefore expected to decrease their effectiveness for enhancing radiotherapy.

Investigation of the dose enhancement effect due to gold nanoparticles at 18 MV radiotherapy using MAGIC-f and Monte Carlo methods Thoraco-Lumbar spinal cord fMRI in 3T Magnetic field

Introduction: Normoxic MAGIC-f polymer gels are established dosimeters used for three dimensional dos uantifications in radiotherapy. The high atomic number nanoparticles such as gold are nov adiosensitizers used to enhance doses delivered to tumors. The aim of this study was t vestigate the effect of gold nanoparticles (GNPs) in enhancing percentage depth doses (PDD ithin the MAGIC-f gel exposed to linac high energy photon beams (18MV). Materials and methods: The MAGIC-f gel was fabricated based on its standard composition with some modifications an oured into falcon tubes. The PDDs in the tubes containing the gel were calculated using a commo onte Carlo code (MCNPX) followed by experimental verifications. Then, the GNPs with a verage diameter of 15 nm and a concentration of 0.1 mM were embedded in the gel, poured int milar falcon tubes and irradiated to 18 MV beams of a Varian 2100 linac. Finally, simila xperimental and Monte Carlo (MC) calculations were conducted to determine the effect of usin e GNPs on some dosimetric parameters of interest. Results: The results of experimental measurements and simulated MC calculations showed a dos nhancement factor (DEF) of 1.12±0.07 and 1.13±0.06 respectively due to the use of the GNP hen exposed to 18 MV linac energies. Conclusion: The results indicated that the fabricated MAGIC-f gel could be recommended as a suitable tool fo ree dimensional dosimetric investigations at high energy radiotherapy procedures wherein th NPs are used.

A framework for e+-e- annihilation detection using nanoparticles for tumour targeting in radiotherapy

The quality of modern patient radiotherapy treatment is strongly dependent on reliable and accurate dosimetry techniques. Although desirable, in situ and in vivo dosimetry is usually hard to implement in routine radiotherapy procedures. The potential use of nanoparticles has been recently considered for biomedical applications achieving promising performance for diagnosis as well as therapeutic practices. The present work reports about a novel proposal based on the use of high atomic number nanoparticles for online estimation of absorbed dose during conventional radiotherapy treatment. In this first phase, the investigation handles with experimental and theoretical tasks regarding the potential use of the variations in the annihilation peak and its correlation with the presence of high atomic number nanoparticles acting as signal enhancers. Dedicated Monte Carlo simulations are also presented in order to complement experimental results and theoretical models. Although the correlation between annihilation peak with the presence of nanoparticles was successfully confirmed, further investigations are still necessary in order to estimate feasible absorbed dose from determinations of annihilation peaks.

Gold nanoparticles enhance radiation sensitization and suppress colony formation in a feline injection site sarcoma cell line, in vitro

Injection Site Sarcomas (ISS) are highly invasive feline malignant tumors that are frequently associated with routine vaccination. Current treatment modalities include chemotherapy, radiation, and radical surgery. ISS have been shown to be one of the most treatment resistant of feline cancers with high rates of recurrence. Previous studies have shown that gold and other high atomic number nanoparticles have the ability to increase the dose of radiation deposited into tissue by generating secondary electrons. The focus of the current study was to assess the effects of gold nanoparticles (AuNP) on ISS cytotoxicity and colony formation both as a standalone treatment and in combination with electron beam radiation. Cells from an established ISS cell line were co-cultured with 15nm AuNP at 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0mM. AuNP cytotoxicity was evaluated by assessing changes in cellularity, cell proliferation, cell cycle and viability/apoptosis/necrosis. The radiosensitizing potential of AuNP on ISS replication was assessed by the clonogenic assay. AuNP were found to significantly decrease cellular proliferation. However, the acute viability and cell cycle of ISS was not significantly altered. Interestingly, AuNP alone were shown to significantly impair colony formation. In the presence of 9MeV electron radiation, AuNP numerically decreased colony formation in ISS cells compared to cells treated with radiation only. AuNP may have efficacy as a long term therapeutic agent for decreasing ISS growth.

Angular dose anisotropy around gold nanoparticles exposed to X-rays

Gold nanoparticle (GNP) radiotherapy has recently emerged as a promising modality in cancer treatment. The use of high atomic number nanoparticles can lead to enhanced radiation dose in tumors due to low-energy leakage electrons depositing in the vicinity of the GNP. A single metric, the dose enhancement ratio has been used in the literature, often in substantial disagreement, to quantify the GNP's capacity to increase local energy deposition. This 1D approach neglects known sources of dose anisotropy and assumes that one average value is representative of the dose enhancement. Whether this assumption is correct and within what accuracy limits it could be trusted, have not been studied due to computational difficulties at the nanoscale. Using a next-generation deterministic computational method, we show that significant dose anisotropy exists which may have radiobiological consequences, and can impact the treatment outcome as well as the development of treatment planning computational methods.

X-ray sensitivity of small organic molecule and zinc cadmium sulfide mixture layers deposited using thermal melting technique

Recently the spin-coating technique was employed to deposit X-ray sensitive layers of polymer mixture with high atomic number nanoparticles. Here, we demonstrate thermal melting method for deposition of X-ray absorptive thick layers. For investigations of X-ray photocurrent the thermally melted layers of various content of N,N,N′,N′-Tetra(p-tolyl) benzidine (TPTB) and Zinc Cadmium Sulfide (ZnCdS) powder have been formed between two ITO-glass and Al-glass substrates. Under X-ray flux of 3.5×109s−1cm−2 the estimated integral dose rates were 2.5mGy/s for pure layer, 38.0mGy/s for 15wt%, 59.8mGy/s for 25wt%, 80.4mGy/s for 35wt% and 108.7mGy/s for 50wt% of ZnCdS in layers. An introduction of ZnCdS particles led to higher conductivity of the layers where the values of reverse bias current estimated up to 75nA/cm2. In the sample with 50wt% ZnCdS, the measured photocurrent (Iph=2.8nA) was almost ten times higher than that in the layer with 15wt% of ZnCdS (0.18). Under low X-ray flux (Φ) Iphvs.Φ dependences deviate from linear while above 2×109s−1cm−2 linear dependences are obtained for all samples. The highest sensitivity is estimated for 50wt% of ZnCdS layer reaching 50nC/mGy/cm3.

Radiosensitising Nanoparticles as Novel Cancer Therapeutics — Pipe Dream or Realistic Prospect?

The field of high atomic number nanoparticle radiosensitising agents is reviewed. After a brief discussion of the new mode of physicochemical action implied by irradiation of high atomic number nanoparticles embedded in biological systems, a series of exemplars are discussed. Silver-, gadolinium- and gold-based nanoparticles are discussed in order of increasing atomic number with functionalisation strategies being outlined. In vitro and in vivo evidence for radio-enhancement and the mechanisms attributed to the increased biological effect are discussed.