Effects of synchrotron-based X-rays and gold nanoparticles on normal and cancer cell morphology and migration.

It has been shown lately that gold nanoparticles (AuNPs) and ionizing radiation (IR) have inhibitory effects on cancer cell migration while having promoting effects on normal cells' motility. Also, IR increases cancer cell adhesion with no significant effects on normal cells. In this study, synchrotron-based microbeam radiation therapy, as a novel pre-clinical radiotherapy protocol, is employed to investigate the effects of AuNPs on cell migration. Experiments were conducted utilizing synchrotron X-rays to investigate cancer and normal cell morphology and migration behaviour when they are exposed to synchrotron broad beams (SBB) and synchrotron microbeams (SMB). This in vitro study was conducted in two phases. In phase I two cancer cell lines - human prostate (DU145) and human lung (A549) - were exposed to various doses of SBB and SMB. Based on the phase I results, in phase II two normal cell lines were studied: human epidermal melanocytes (HEM) and human primary colon epithelial (CCD841), along with their respective cancerous counterparts, human primary melanoma (MM418-C1) and human colorectal adenocarcinoma (SW48). The results show that radiation-induced damage in cells' morphology becomes visible with SBB at doses greater than 50 Gy, and incorporating AuNPs increases this effect. Interestly, under the same conditions, no visible morphological changes were observed in the normal cell lines post-irradiation (HEM and CCD841). This can be attributed to the differences in cell metabolic and reactive oxygen species levels between normal and cancer cells. The outcome of this study highlights future applications of synchrotron-based radiotherapy, where it is possible to deliver extremely high doses to cancer tissues whilst preserving surrounding normal tissues from radiation-induced damage.

Oxidative Damage to Mitochondria Enhanced by Ionising Radiation and Gold Nanoparticles in Cancer Cells.

Gold nanoparticles (AuNP) can increase the efficacy of radiation therapy by sensitising tumor cells to radiation damage. When used in combination with radiation, AuNPs enhance the rate of cell killing; hence, they may be of great value in radiotherapy. This study assessed the effects of radiation and AuNPs on mitochondrial reactive oxygen species (ROS) generation in cancer cells as an adjunct therapeutic target in addition to the DNA of the cell. Mitochondria are considered one of the primary sources of cellular ROS. High levels of ROS can result in an intracellular state of oxidative stress, leading to permanent cell damage. In this study, human melanoma and prostate cancer cell lines, with and without AuNPs, were irradiated with 6-Megavolt X-rays at doses of 0-8 Gy. Indicators of mitochondrial stress were quantified using two techniques, and were found to be significantly increased by the inclusion of AuNPs in both cell lines. Radiobiological damage to mitochondria was quantified via increased ROS activity. The ROS production by mitochondria in cells was enhanced by the inclusion of AuNPs, peaking at ~4 Gy and then decreasing at higher doses. This increased mitochondrial stress may lead to more effectively kill of AuNP-treated cells, further enhancing the applicability of functionally-guided nanoparticles.

Differential Effects of Gold Nanoparticles and Ionizing Radiation on Cell Motility between Primary Human Colonic and Melanocytic Cells and Their Cancerous Counterparts.

This study examined the effects of gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the viability and motility of human primary colon epithelial (CCD841) and colorectal adenocarcinoma (SW48) cells as well as human primary epidermal melanocytes (HEM) and melanoma (MM418-C1) cells. AuNPs up to 4 mM had no effect on the viability of these cell lines. The viability of the cancer cells was ~60% following exposure to 5 Gy. Exposure to 5 Gy X-rays or 1 mM AuNPs showed the migration of the cancer cells ~85% that of untreated controls, while co-treatment with AuNPs and IR decreased migration to ~60%. In the non-cancerous cell lines gap closure was enhanced by ~15% following 1 mM AuNPs or 5 Gy treatment, while for co-treatment it was ~22% greater than that for the untreated controls. AuNPs had no effect on cell re-adhesion, while IR enhanced only the re-adhesion of the cancer cell lines but not their non-cancerous counterparts. The addition of AuNPs did not enhance cell adherence. This different reaction to AuNPs and IR in the cancer and normal cells can be attributed to radiation-induced adhesiveness and metabolic differences between tumour cells and their non-cancerous counterparts.

Nanoparticle dose enhancement of synchrotron radiation in PRESAGE dosimeters.

The physical absorbed dose enhancement by the inclusion of gold and bismuth nanoparticles fabricated into water-equivalent PRESAGE dosimeters was investigated. Nanoparticle-loaded water-equivalent PRESAGE dosimeters were irradiated with superficial, synchrotron and megavoltage X-ray beams. The change in optical density of the dosimeters was measured using UV-Vis spectrophotometry pre- and post-irradiation using a wavelength of 630 nm. Dose enhancement was measured for 5 nm and 50 nm monodispersed gold nanoparticles, 5-50 nm polydispersed bismuth nanoparticles, and 80 nm monodispersed bismuth nanoparticles at concentrations from 0.25 mM to 2 mM. The dose enhancement was highest for the 95.3 keV mean energy synchrotron beam (16-32%) followed by the 150 kVp superficial beam (12-21%) then the 6 MV beam (2-5%). The bismuth nanoparticle-loaded dosimeters produced a larger dose enhancement than the gold nanoparticle-loaded dosimeters in the synchrotron beam for the same concentration. For the superficial and megavoltage beams the dose enhancement was similar for both species of nanoparticles. The dose enhancement increased with nanoparticle concentration in the dosimeters; however, there was no observed nanoparticle size dependence on the dose enhancement.

Combined Effects of Gold Nanoparticles and Ionizing Radiation on Human Prostate and Lung Cancer Cell Migration.

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration. The relative migration of cells irradiated with 5 Gy was found to be 89% and 86% for DU145 and A549 cells respectively. When the cells were treated with 1 mM AuNPs this fell to ~75% for both cell lines. However, when the cells were treated with both AuNPs and IR an additive effect was seen, as the relative migration rate fell to ~60%. Of interest was that when the cells were exposed to either 2 or 5 Gy IR, their ability to adhere to the surface of a polystyrene culture plate was significantly enhanced, unlike that seen for AuNPs. The delays in gap filling (cell migration) in cells treated with IR and/or AuNPs can be attributed to cellular changes which also may have altered cell motility. In addition, changes in the cytoskeleton of the cancer cells may have also affected adhesiveness and thus the cancer cell's motility response to IR.

On the use of AAA and AcurosXB algorithms for three different stereotactic ablative body radiotherapy (SABR) techniques: Volumetric modulated arc therapy (VMAT), intensity modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3D-CRT).

AIM: The purpose of this study was to investigate the dosimetric characteristics of three stereotactic ablative body radiotherapy (SABR) techniques using the anisotropic analytical algorithm (AAA) and Acuros XB algorithm. The SABR techniques include coplanar volumetric modulated arc therapy (C-VMAT), non-coplanar intensity modulated radiation therapy (NC-IMRT) and non-coplanar three-dimensional conformal radiotherapy (NC-3D CRT). BACKGROUND: SABR is a special type of radiotherapy where a high dose of radiation is delivered over a short time. The treatment outcome and accuracy of the dose delivered to cancer patients highly depend on the dose calculation algorithm and treatment technique. MATERIALS AND METHODS: Twelve lung cancer patients underwent 4D CT scanning, and three different treatment plans were generated: C-VMAT, NC-IMRT, NC-3D CRT. Dose calculation was performed using the AAA and Acuros XB algorithm. The dosimetric indices, such as conformity index (CI), homogeneity index, dose fall-off index, doses received by organs at risk and planning target volume, were used to compare the plans. The accuracy of AAA and Acuros XB (AXB) algorithms for the lung was validated against measured dose on a CIRS thorax phantom. RESULTS: The CIs for C-VMAT, NC-IMRT and NC-3D CRT were 1.21, 1.28 and 1.38 for the AAA, respectively, and 1.17, 1.26 and 1.36 for the Acuros XB algorithm, respectively. The overall dose computed by AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm. The overall dose computed by the AcurosXB algorithm was close to the measured dose when compared to the AAA algorithm. CONCLUSION: This study showed that the treatment planning results obtained using the Acuros XB algorithm was better than those using the AAA algorithm in SABR lung radiotherapy.

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours.

AIM: To investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours. BACKGROUND: In the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment. MATERIALS AND METHODS: Data were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment. RESULTS: The mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes. CONCLUSIONS: More caution and an additional safety margins are required when tracking a single fiducial marker.

Titanium Dioxide Nanoparticles as Radiosensitisers: An In vitro and Phantom-Based Study.

Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO2-NPs) is investigated using phantoms (PRESAGE® dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells. Methods: Anatase TiO2-NPs were synthesised, characterised and functionalised to allow dispersion in culture-medium for in vitro studies and halocarbons (PRESAGE® chemical compositions). PRESAGE® dosimeters were scanned with spectrophotometer to determine the radiation dose enhancement. Clonogenic and cell viability assays were employed to determine cells survival curves from which the dose enhancement levels "radiosensitisation" are deduced. Results: Comparable levels of radiosensitisation were observed in both phantoms and cells at kilovoltage ranges of x-ray energies (slightly higher in vitro). Significant radiosensitisation (~67 %) of control was also noted in cells at megavoltage energies (commonly used in radiotherapy), compared to negligible levels detected by phantoms. This difference is attributed to biochemical effects, specifically the generation of reactive oxygen species (ROS) such as hydroxyl radicals (•OH), which are only manifested in aqueous environments of cells and are non-existent in case of phantoms. Conclusions: This research shows that TiO2-NPs improve the efficiency of dose delivery, which has implications for future radiotherapy treatments. Literature shows that Ti2O3-NPs can be used as imaging agents hence with these findings renders these NPs as theranostic agents.

Dosimetric impact of VMAT delivery angles for early glottic cancer treatment.

This study investigates the dosimetric effects of different gantry rotation angles used in volumetric modulated arc therapy (VMAT) for early glottic carcinoma. VMAT treatment plans using full-arc, half-arc, and partial-arc gantry rotation angles were generated from 22 computed tomography datasets of early-stage (T1-2N0) glottic laryngeal cancer. Dosimetric parameters associated with the planning target volume (PTV) and organs at risk (OARs), specifically the carotid arteries and thyroid, were compared. To assess the robustness of the VMAT plans, dose variations were analyzed by introducing positional shifts of 1, 3, and 5 mm from the isocenter of each plan along the superior-inferior, left-right, and anterior-posterior axes. Furthermore, we examined the size of the PTV, the air cavity volume within the PTV, and the variability of the beam path length through the gantry angles to investigate their correlations with PTV dose variations in the presence of positioning errors. Compared to full-arc and half-arc plans, the dosimetric parameters of partial-arc plans were found to be higher in PTV (D2%, D5%, D50%, and Dmean) and lower in OARs, while their dose variations of OAR parameters were greater for positioning errors. In addition, a correlation was observed between PTV size and PTV dose variations. Air cavity volume and depth variability were also correlated with some PTV parameters, depending on the arc plan. The results presented in this study suggest that the partial-arc gantry angles can allow higher PTV doses while minimizing OAR doses in VMAT treatment planning for early glottic cancer. However, the small delivery angles may lead to greater dose variations in the OARs when positioning errors occur.

Ultrasound-stimulated microbubbles to enhance radiotherapy: A scoping review.

INTRODUCTION: Primarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be 'burst' to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound-stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action. METHODS: Primary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action. RESULTS: Overall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action. CONCLUSIONS: USMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to target all three phases of radiation action.

The impact of fluorine-18-fluoroethyltyrosine positron emission tomography scan timing on radiotherapy planning in newly diagnosed patients with glioblastoma.

Background and purpose: Glioblastoma is one of the most common and aggressive primary brain tumours in adults. Though radiation therapy (RT) techniques have progressed significantly in recent decades, patient survival has seen little improvement. However, an area of promise is the use of fluorine-18-fluoroethyltyrosine positron-emission-tomography (18F-FET PET) imaging to assist in RT target delineation. This retrospective study aims to assess the impact of 18F-FET PET scan timing on the resultant RT target volumes and subsequent RT plans in post-operative glioblastoma patients. Materials and Methods: The imaging and RT treatment data of eight patients diagnosed with glioblastoma and treated at a single institution were analysed. Before starting RT, each patient had two 18F-FET-PET scans acquired within seven days of each other. The information from these 18F-FET-PET scans aided in the creation of two novel target volume sets. The new volumes and plans were compared with each other and the originals. Results: The median clinical target volume (CTV) 1 was statistically smaller than CTV 2. The median Dice score for the CTV1/CTV2 was 0.98 and, of the voxels that differ (median 6.5 cc), 99.7% were covered with a 5 mm expansion. Overall organs at risk (OAR) and target dosimetry were similar in the PTV1 and PTV2 plans. Conclusion: Provided the 18F-FET PET scan is acquired within two weeks of the RT planning and a comprehensive approach is taken to CTV delineation, the timing of scan acquisition has minimal impact on the resulting RT plan.

Measuring dose in lung identifies peripheral tumour dose inaccuracy in SBRT audit.

PURPOSE: Stereotactic Body Radiotherapy (SBRT) for lung tumours has become a mainstay of clinical practice worldwide. Measurements in anthropomorphic phantoms enable verification of patient dose in clinically realistic scenarios. Correction factors for reporting dose to the tissue equivalent materials in a lung phantom are presented in the context of a national dosimetry audit for SBRT. Analysis of dosimetry audit results is performed showing inaccuracies of common dose calculation algorithms in soft tissue lung target, inhale lung material and at tissue interfaces. METHODS: Monte Carlo based simulation of correction factors for detectors in non-water tissue was performed for the soft tissue lung target and inhale lung materials of a modified CIRS SBRT thorax phantom. The corrections were determined for Gafchromic EBT3 Film and PTW 60019 microDiamond detectors used for measurements of 168 SBRT lung plans in an end-to-end dosimetry audit. Corrections were derived for dose to medium (Dm,m) and dose to water (Dw,w) scenarios. RESULTS: Correction factors were up to -3.4% and 9.2% for in field and out of field lung respectively. Overall, application of the correction factors improved the measurement-to-plan dose discrepancy. For the soft tissue lung target, agreement between planned and measured dose was within average of 3% for both film and microDiamond measurements. CONCLUSIONS: The correction factors developed for this work are provided for clinical users to apply to commissioning measurements using a commercially available thorax phantom where inhomogeneity is present. The end-to-end dosimetry audit demonstrates dose calculation algorithms can underestimate dose at lung tumour/lung tissue interfaces by an average of 2-5%.

Polymer gels impregnated with gold nanoparticles implemented for measurements of radiation dose enhancement in synchrotron and conventional radiotherapy type beams.

Normoxic type polyacrylamide gel (nPAG) dosimeters are established for dose quantification in three-dimensions for radiotherapy and hence represent an adequate dosimeter for quantification of the dose variation due to the existence of the gold nanoparticles (AuNPs) in the target during irradiation. This work compared the degree of polymerisation in gel doped with nanoparticles (nPAG-AuNP) with control gel samples when irradiated by various sources. Samples were irradiated with a synchrotron radiation source of mean energy 125 keV, 80 kV X-ray beams from superficial therapy machine (SXRT), 6 MV X-rays and 6 MeV electron beams from linear accelerator. Analysis of the dose-response relation was used to determine a dose enhancement factor (DEF) of 1.76 ± 0.34 and 1.64 ± 0.44 obtained for samples irradiated with kilovoltage X-rays energy from synchrotron source and SXRT respectively. Similarly, including AuNPs in gel results in a DEF of approximately 1.37 ± 0.35 when irradiated by an electron beam and 1.14 ± 0.28 for high energy X-ray beams. The results demonstrate the use of AuNPs embedded in polymer gels for measuring the enhancement of radiation caused by metallic nanoparticles.

Ultrasound-Stimulated Microbubbles Enhance Radiation-Induced Cell Killing.

Recent in vivo studies using ultrasound-stimulated microbubbles as a localized radiosensitizer have had impressive results. While in vitro studies have also obtained similar results using human umbilical vein endothelial cells (HUVEC), studies using other cell lines have had varying results. This study was aimed at investigating any increases in radiation-induced cell killing in vitro using two carcinoma lines not previously investigated before (metastatic follicular thyroid carcinoma cells [FTC-238] and non-small cell lung carcinoma cells [NCI-H727]), in addition to HUVEC. Cells were treated using a combination of 1.6% (v/v) microbubbles, ∼90 s of 2-MHz ultrasound (mechanical index = 0.8) and 0-6 Gy of kilovolt or MV X-rays. Cell viability assays obtained 72 h post-treatment were normalized to untreated controls, and analysis of variance was used to determine statistical significance. All cells treated with combined ultrasound-stimulated microbubbles and radiation exhibited decreased normalized survival, with statistically significant effects observed for the NCI-H727 cells. No statistically significant differences in effects were observed using kV compared with MV radiation. Further studies using increased microbubble concentrations may be required to achieve statistically significant results for the FTC-238 and HUVEC lines.

Dose assessment for daily cone-beam CT in lung radiotherapy patients and its combination with treatment planning.

With the increased use of X-ray imaging for patient alignment in external beam radiation therapy, particularly with cone-beam computed tomography (CBCT), the additional dose received by patients has become of greater consideration. In this study, we analysed the radiation dose from CBCT for clinical lung radiotherapy and assessed its relative contribution when combined with radiation treatment planning for a variety of lung radiotherapy techniques. The Monte Carlo simulation program ImpactMC was used to calculate the 3D dose delivered by a Varian TrueBeam linear accelerator to patients undergoing thorax CBCT imaging. The concomitant dose was calculated by simulating the daily CBCT irradiation of ten lung cancer patients. Each case was planned with a total dose of 50-60 Gy to the target lesion in 25-30 fractions using the 3DCRT or IMRT plan and retrospectively planned using VMAT. For each clinical case, the calculated CBCT dose was summed with the planned dose, and the dose to lungs, heart, and spinal cord were analysed according to conventional dose conformity metrics. Our results indicate greater variations in dose to the heart, lungs, and spinal cord based on planning technique, (3DCRT, IMRT, VMAT) than from the inclusion of daily cone-beam imaging doses over 25-30 fractions. The average doses from CBCT imaging per fraction to the lungs, heart and spinal cord were 0.52 ± 0.10, 0.49 ± 0.15 and 0.39 ± 0.08 cGy, respectively. Lung dose variations were related to the patient's size and body composition. Over a treatment course, this may result in an additional mean absorbed dose of 0.15-0.2 Gy. For lung V5, the imaging dose resulted in an average increase of ~ 0.6% of the total volume receiving 5 Gy. The increase in V20 was more dependent on the planning technique, with 3DCRT increasing by 0.11 ± 0.09% with imaging and IMRT and VMAT increasing by 0.17 ± 0.05% and 0.2 ± 0.06%, respectively. In this study, we assessed the concomitant dose for daily CBCT lung cancer patients undergoing radiotherapy. The additional radiation dose to the normal lungs from daily CBCT was found to range from 0.15 to 0.2 Gy when the patient was treated with 25-30 fractions. Consideration of potential variation in relative biological effectiveness between kilovoltage imaging and megavoltage treatment dose was outside the scope of this study. Regardless of this, our results show that the assessment of imaging dose can be incorporated into the treatment planning process and the relative effect on overall dose distribution was small compared to the difference among planning techniques.

Functional brain imaging interventions for radiation therapy planning in patients with glioblastoma: a systematic review.

RATIONALE: This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research. METHODS: The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle-Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions. RESULTS: There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72-76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm[Formula: see text]. CONCLUSION: There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the clinical target volume when designing radiation therapy plans for patients with glioblastoma.

Natural Baicalein-Rich Fraction as Radiosensitizer in Combination with Bismuth Oxide Nanoparticles and Cisplatin for Clinical Radiotherapy.

Purpose: Chemotherapy has been used in conjunction with radiation therapy to improve the treatment outcomes of cancers. Cisplatin (Cis) is a standard treatment that has been used as a chemotherapeutic drug in medical settings. However, the possibility of complications constrains the treatment due to the exposure of healthy organs to unnecessary radiation and the drugs' toxicities. As a result, researchers have been looking for non-toxic chemotherapeutic agents which can be used as radiosensitizers, possibly produced from natural derivatives and nano sized materials. Methods: BRF, Cis, and BiONPs were irradiated individually and in combinations with 6 MV of photon beam and 6 MeV of electron beams with 0 to 10 Gy radiation doses on MCF-7, MDA-MB-231, and NIH/3T3 cell lines. Then, the experimental sensitization enhancement ratios (SER) of each treatment obtained were compared to the theoretical dose enhancement factor (DEF). The interactions within the BRF-BiONPs (BB) and BRF-Cis-BiONPs (BCB) combinations were also estimated using the Combination Index (CI). Results: BRF induced radiosensitization in all cells under 6 MV photon beam (SER of 1.06 to 1.35), and MDA-MB-231 cells only under 6 MeV electron beam (SER = 1.20). The highest SER values for BiONPs and Cis were obtained from MCF-7 cells under a 6 MeV electron beam (SER of 1.50 and 2.24, respectively). The theoretical DEFs were generally lower than the experimental SERs. Based on the SER and CI relationships, it was estimated that BB and BCB therapy methods interacted in either a synergistic or additive manner. Conclusion: The BRF is found to induce relatively less radiosensitization effects compared to the BiONPs and Cis. The BB and BCB combinations have shown better effects with potential for becoming competently suitable radiosensitizers in breast cancer therapies.

Evaluation of the effects of gold nanoparticle shape and size on contrast enhancement in radiological imaging.

There has been increasing interest in the use of a nanoparticle-based media as a contrast-enhancement agent in medical imaging, particularly with gold Nanoparticles in radiography. Particularly attractive, is the prospect of modifying the surface of these materials with monoclonal antibodies to preferentially bind the nanoparticles to tumour sites. These materials differ from conventional molecular agents in their ability to be modified with cell specificity, or tailored for size and shape for maximum uptake. We investigated the consideration that quantum confinement electronic effects in nanometre-sized metals might have an effect on the integrated photon attenuation of gold atoms; in the same manner as these materials affect X-ray absorption and scattering as seen in X-ray absorption spectroscopy. This experiment has been designed to identify any effect on contrast enhancement that might result from employing gold nanoparticles with a variety of sizes. Spherical particles and nanorods were synthesised for this application. Image contrast enhancement was quantified by contrast-to-noise ratio in computed radiography. Results are consistent with existing measurements of gold nanoparticle contrast enhancement in radiography. No significant variation in attenuation depending on particle size was observed. Findings indicate that nanoparticle-based contrast agents in the size range 4-30 nm-can be synthesised for maximum stability or cell specificity (directed cellular uptake) without consideration of effect of size on contrast enhancement.

Quantifying the effects of iodine contrast media on standardised uptake values of FDG PET/CT images: an anthropomorphic phantom study.

This study aimed to quantify the amount of change in Standardised Uptake Values (SUVs) of PET/CT images by simulating the set-up as closely as possible to the actual patient scanning. The experiments were conducted using an anthropomorphic phantom, which contained an amount of radioactivity in the form of Fluorodeoxyglucose (FDG) in a primary plastic test tube and one litre saline bags, including the insertion of bony structures and another two test tubes containing different concentrations of iodine contrast media. Standard scanning protocols were employed for the PET/CT image acquisition. The highest absolute differences in the SUVmax and SUVmean values of the saline bags were found to be about 0.2 and 0.4, respectively. The primary test tube showed the largest change of 1.5 in both SUVs; SUV max and SUVmean. However, none of these changes were found to be statistically significant. The clinical literature also contains no evidence to suggest that the changes of this magnitude would change the final diagnosis. Based on these preliminary data, we propose that iodine contrast media can be used during the CT scan of PET/CT imaging, without significantly affecting the diagnostic quality of this integrated imaging modality.

SABR pre-treatment checks using alanine and nanoDot dosimeters.

Stereotactic Ablative Radiotherapy (SABR) remains one of the preferred treatment techniques for early-stage cancer. It can be extended to more treatment locales involving the sternum, scapula and spine. This work investigates SABR checks using Alanine and nanoDot dosimeter for three treatment sites, including sternum, spine and scapula. Alanine and nanoDot dosimeters' performances were verified using a 6 MV photon beam before SABR pretreatment verifications. Each dosimeter was placed inside customized designed inserts into a Rod Phantom (in-house phantom) made of Perspex that mimics the human body for a SABR check. Electron Paramagnetic Resonance (EPR) spectrometer, Bruker EleXsys E500 (9.5 GHz) and Microstar (Landauer Inc.) Reader was employed to acquire the irradiated alanine and nanoDot dosimeters' signal, respectively. Both dosimeters treatment sites are expressed as mean ± standard deviation (SD) of the measured and Eclipse calculated dose Alanine (19.59 ± 0.24, 17.98 ± 0.15, 17.95 ± 0.18) and nanoDot (19.70 ± 0.43, 17.05 ± 0.08, 17.95 ± 0.98) for spine, scapula and sternum, respectively. The percentage difference between alanine and nanoDot dosimeters was within 2% for sternum and scapula but 2.4% for spine cases. These results demonstrate Alanine and nanoDot dosimeters' potential usefulness for SABR pretreatment quality assurance (QA).