Improvement of performance for flexible film dosimeter by incorporating additive agents.

Objective.To evaluate the reduction in energy dependence and aging effect of the lithium salt of pentacosa-10,-12-diynoic acid (LiPCDA) films with additives including aluminum oxide (Al2O3), propyl gallate (PG), and disodium ethylenediaminetetracetate (EDTA).Approach. LiPCDA films exhibited energy dependence on kilovoltage (kV) and megavoltage (MV) photon energies and experienced deterioration over time. Evaluations were conducted with added Al2O3and antioxidants to mitigate these issues, and films were produced with and without Al2O3to assess energy dependence. The films were irradiated at doses of 0, 3, 6, and 12 cGy at photon energies of 75 kV, 105 kV, 6 MV, 10 MV, and 15 MV. For the energy range of 75 kV to 15 MV, the mean and standard deviation (std) were calculated and compared for the values normalized to the net optical density (netOD) at 6 MV, corresponding to identical dose levels. To evaluate the aging effect, PG and disodium EDTA were incorporated into the films: sample C with 1% PG, sample D with 2% PG, sample E with 0.62% disodium EDTA added to sample D, and sample F with 1.23% disodium EDTA added to sample D.Main results. Films containing Al2O3demonstrated a maximum 15.8% increase in mean normalized values and a 15.1% reduction in std, reflecting a greater netOD reduction at kV than MV energies, which indicates less energy dependence in these films. When the OD of sample 1-4 depending on the addition of PG and disodium EDTA, was observed for 20 weeks, the transmission mode decreased by 8.7%, 8.3%, 29.3%, and 27.3%, respectively, while the reflection mode was 5.4%, 3.0%, 37.0%, and 34.5%, respectively.Significance. Al2O3effectively reduced the voltage and MV energy dependence. PG was more effective than disodium EDTA in preventing the deterioration of film performance owing to the aging effect.

Conversion of single-energy computed tomography to parametric maps of dual-energy computed tomography using convolutional neural network.

OBJECTIVES: We propose a deep learning (DL) multi-task learning framework using convolutional neural network (CNN) for a direct conversion of single-energy CT (SECT) to three different parametric maps of dual-energy CT (DECT): Virtual-monochromatic image (VMI), effective atomic number (EAN), and relative electron density (RED). METHODS: We propose VMI-Net for conversion of SECT to 70, 120, and 200 keV VMIs. In addition, EAN-Net and RED-Net were also developed to convert SECT to EAN and RED. We trained and validated our model using 67 patients collected between 2019 and 2020. SECT images with 120 kVp acquired by the DECT (IQon spectral CT, Philips) were used as input, while the VMIs, EAN, and RED acquired by the same device were used as target. The performance of the DL framework was evaluated by absolute difference (AD) and relative difference (RD). RESULTS: The VMI-Net converted 120 kVp SECT to the VMIs with AD of 9.02 Hounsfield Unit, and RD of 0.41% compared to the ground truth VMIs. The ADs of the converted EAN and RED were 0.29 and 0.96, respectively, while the RDs were 1.99% and 0.50% for the converted EAN and RED, respectively. CONCLUSIONS: SECT images were directly converted to the three parametric maps of DECT (ie, VMIs, EAN, and RED). By using this model, one can generate the parametric information from SECT images without DECT device. Our model can help investigate the parametric information from SECT retrospectively. ADVANCES IN KNOWLEDGE: Deep learning framework enables converting SECT to various high-quality parametric maps of DECT.

Evaluations of patient-specific bolus fabricated by mold-and-cast method using computer numerical control machine tools†.

The patient-specific bolus fabricated by a mold-and-cast method using a 3D printer (3DP) and silicon rubber has been adopted in clinical practices. Manufacturing a mold using 3DP, however, can cause time delays due to failures during the 3D printing process. Thereby, we investigated an alternative method of the mold fabrication using computer numerical control (CNC) machine tools. Treatment plans were conducted concerning a keloid scar formed on the ear and nose. The bolus structures were determined in a treatment planning system (TPS), and the molds were fabricated using the same structure file but with 3DP and CNC independently. Boluses were then manufactured using each mold with silicone rubbers. We compared the geometrical difference between the boluses and the planned structure using computed tomography (CT) images of the boluses. In addition, dosimetric differences between the two measurements using each bolus and the differences between the measured and calculated dose from TPS were evaluated using an anthropomorphic head phantom. Geometrically, the CT images of the boluses fabricated by the 3DP mold and the CNC mold showed differences compared to the planned structure within 2.6 mm of Hausdorff distance. The relative dose difference between the measurements using either bolus was within 2.3%. In conclusion, the bolus made by the CNC mold benefits from a stable fabricating process, retaining the performance of the bolus made by the 3DP mold.

Novel tongue-positioning device to reduce tongue motions during radiation therapy for head and neck cancer: Geometric and dosimetric evaluation.

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue.

Development of a quasi-3D dosimeter using radiochromic plastic for patient-specific quality assurance.

BACKGROUND: Patient-specific QA verification ensures patient safety and treatment by verifying radiation delivery and dose calculations in treatment plans for errors. However, a two-dimensional (2D) dose distribution is insufficient for detecting information on the three-dimensional (3D) dose delivered to the patient. In addition, 3D radiochromic plastic dosimeters (RPDs) such as PRESAGE® represent the volume effect in which the dosimeters have different sensitivities according to the size of the dosimeters. Therefore, to solve the volume effect, a Quasi-3D dosimetry system was proposed to perform patient-specific QA using predetermined-sized and multiple RPDs. PURPOSE: For patient-specific quality assurance (QA) in radiation treatment, this study aims to assess a quasi-3D dosimetry system using an RPD. METHODS: Gamma analysis was performed to verify the agreement between the measured and estimated dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). We fabricated cylindrical RPDs and a quasi-3D dosimetry phantom. A practicability test for a pancreatic patient utilized a quasi-3D dosimetry device, an in-house RPD, and a quasi-3D phantom. The dose distribution of the VMAT design dictated the placement of nine RPDs. Moreover, a 2D diode array detector was used for 2D gamma analysis (MapCHECK2). The patient-specific QA was performed for IMRT, VMAT, and stereotactic ablative radiotherapy (SABR) in 20 prostate and head-and-neck patients. For each patient, six RPDs were positioned according to the dose distribution. VMAT SABR and IMRT/VMAT plans employed a 2%/2 mm gamma criterion, whereas IMRT/VMAT plans used a 3%/2 mm gamma criterion, a 10% threshold value, and a 90% passing rate tolerance. 3D gamma analysis was conducted using the 3D Slicer software. RESULTS: The average gamma passing rates with 2%/2 mm and 3%/3 mm criteria for relative dose distribution were 91.6% ± 1.4% and 99.4% ± 0.7% for the 3D gamma analysis using the quasi-3D dosimetry system, respectively, and 97.5% and 99.3% for 2D gamma analysis using MapCHECK2, respectively. The 3D gamma analysis for patient-specific QA of 20 patients showed passing rates of over 90% with 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. CONCLUSIONS: The quasi-3D dosimetry system was evaluated by performing patient-specific QAs with RPDs and quasi-3D phantom. The gamma indices for all RPDs showed more than 90% for 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. We verified the feasibility of a quasi-3D dosimetry system by performing the conventional patient-specific QA with the quasi-3D dosimeters.

Extension of matRad with a modified microdosimetric kinetic model for carbon ion treatment planning: Comparison with Monte Carlo calculation.

BACKGROUND: Treatment planning is essential for in silico particle therapy studies. matRad is an open-source research treatment planning system (TPS) based on the local effect model, which is a type of relative biological effectiveness (RBE) model. PURPOSE: This study aims to implement a microdosimetric kinetic model (MKM) in matRad and develop an automation algorithm for Monte Carlo (MC) dose recalculation using the TOPAS code. In addition, we provide the developed MKM extension as open-source tool for users. METHODS: Carbon beam data were generated using TOPAS MC pencil beam irradiation. We parameterized the TOPAS MC beam data with a double-Gaussian fit and modeled the integral depth doses and lateral spot profiles in the range of 100-430 MeV/u. To implement the MKM, the specific energy data table for Z = 1-6 and integrated depth-specific energy data were acquired based on the Kiefer-Chatterjee track structure and TOPAS MC simulation, respectively. Generic data were integrated into matRad, and treatment planning was performed based on these data. The optimized plan parameters were automatically converted into MC simulation input. Finally, the matRad TPS and TOPAS MC simulations were compared using the RBE-weighted dose calculation results. A comparison was made for three geometries: homogeneous water phantom, inhomogeneous phantom, and patient. RESULTS: The RBE-weighted dose (DRBE ) distribution agreed with TOPAS MC within 1.8% for all target sizes for the homogeneous phantom. For the inhomogeneous phantom, the relative difference in the range of 80% of the prescription dose in the distal fall-off region (R80) between the matRad TPS and TOPAS MC was 0.6% (1.1 mm). DRBE between the TPS and the MC was within 4.0%. In the patient case, the difference in the dose-volume histogram parameters for the target volume between the TPS and the MC was less than 2.7%. The relative difference in R80 was 0.7% (1.2 mm). CONCLUSIONS: The MKM was successfully implemented in matRad TPS, and the RBE-weighted dose was comparable to that of TOPAS MC. The MKM-implemented matRad was released as an open-source tool. Further investigations with MC simulations can be conducted using this tool, providing a good option for carbon ion research.

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Performance evaluation of a visual guidance patient-controlled respiratory gating system for respiratory-gated magnetic-resonance image-guided radiation therapy.

The performance of a visual guidance patient-controlled (VG-PC) respiratory gating system for magnetic-resonance (MR) image-guided radiation therapy (MR-IGRT) was evaluated through a clinical trial of patients with either lung or liver cancer. Patients can voluntarily control their respiration utilizing the VG-PC respiratory gating system. The system enables patients to view near-real-time cine planar MR images projected inside the bore of MR-IGRT systems or an external screen. Twenty patients who had received stereotactic ablative radiotherapy (SABR) for lung or liver cancer were prospectively selected for this study. Before the first treatment, comprehensive instruction on the VG-PC respiratory gating system was provided to the patients. Respiratory-gated MR-IGRT was performed for each patient with it in the first fraction and then without it in the second fraction. For both the fractions, the total treatment time, beam-off time owing to the respiratory gating, and number of beam-off events were analyzed. The average total treatment time, beam-off time, and number of beam-off events with the system were 1507.3 s, 679.5 s, and 185, respectively, and those without the system were 2023.7 s (p < 0.001), 1195.0 s (p < 0.001), and 380 times (p < 0.001), respectively. The VG-PC respiratory gating system improved treatment efficiency through a reduction in the beam-off time, the number of beam-off events, and consequently the total treatment time when performing respiratory-gated MR-IGRT for lung and liver SABR.

Scanning methodology for contact lens-type ocular in vivo dosimeter (CLOD) dosimetry applying a silicone material.

PURPOSE: Contact lens-type ocular in vivo dosimeters (CLODs) were recently developed as the first in vivo dosimeter that can be worn directly on the eye to measure the dose delivered to the lens during radiotherapy. However, it has an inherent uncertainty because of its curved shape. Newton's ring effect inevitably occurs because the spacing between the glass window and the active layer is not constant. Furthermore, it involves a large uncertainty because the objective of the CLOD with such morphological characteristics is to measure the dose delivered to an out-of-field lens. In this study, we aimed to investigate the effects of various compensating materials on the sensitivity, accuracy, and uniformity of analysis using a curved CLOD. We developed a new scanning methodology that involves applying a compensating material to reduce the uncertainty caused by the air gap. METHODS: Four compensating materials-Dragon Skin™ 10 (DS), a transparent silicon material, SORTA-Clear™ 40 (SC), optical grease (OG), and air (no compensating material)-were used in this study. The CLOD was scanned in the reflective mode and transmission mode using each compensating material. We then examined the sensitivity, accuracy, and scan uniformity to evaluate the scanning methodology using compensating materials. RESULTS: The increase in sensitivity was the highest for OG compared to that for air in the reflective mode. On average, the sensitivity in the reflective mode was higher than that in the transmission mode by a factor of 2.5 for each dose. Among the four compensating materials, OG had the smallest uncertainty. Therefore, the best scan uniformity was achieved when OG was used. CONCLUSIONS: Scanning methodology was proposed in which a compensating material is applied for a curved lens-type dosimeter. Our results show that OG is the most suitable compensating material to obtain the best accuracy of dose analysis. Following this methodology, the scan uncertainty of curved dosimeters significantly decreased.

3D star shot analysis using MAGAT gel dosimeter for integrated imaging and radiation isocenter verification of MR-Linac system.

PURPOSE: This study aims to investigate a star shot analysis using a three-dimensional (3D) gel dosimeter for the imaging and radiation isocenter verification of a magnetic resonance linear accelerator (MR-Linac). METHODS: A mixture of methacrylic acid, gelatin, and tetrakis (hydroxymethyl) phosphonium chloride, called MAGAT gel, was fabricated. One MAGAT gel for each Linac and MR-Linac was irradiated under six gantry angles. A 6 MV photon beam of Linac and a 6 MV flattening filter free beam of MR-Linac were delivered to two MAGAT gels and EBT3 films. MR images were acquired by MR-Linac with a clinical sequence (i.e., TrueFISP). The 3D star shot analysis for seven consecutive slices of the MR images with TrueFISP was performed. The 2D star shot analysis for the central plane of the gel was compared to the results from the EBT3 films. The radius of isocircle (ICr ) and the distance between the center of the circle and the center marked on the image (ICd ) were evaluated. RESULTS: For MR-Linac with MAGAT gel measurements, ICd at the central plane was 0.46 mm for TrueFISP. Compared to EBT3 film measurements, the differences in ICd and ICr for both Linac and MR-Linac were within 0.11 and 0.13 mm, respectively. For the 3D analysis, seven consecutive slices of TrueFISP images were analyzed and the maximum radii of isocircles (ICr_max ) were 0.18 mm for Linac and 0.73 mm for MR-Linac. The tilting angles of radiation axis were 0.31° for Linac and 0.10° for MR-Linac. CONCLUSION: The accuracy of 3D star shot analysis using MAGAT gel was comparable to that of EBT3 film, having a capability for integrated analysis for imaging isocenter and radiation isocenter. 3D star shot analysis using MAGAT gel can provide 3D information of radiation isocenter, suggesting a quantitative extent of gantry-tilting.

Comparison of treatment plans between static jaw and jaw tracking techniques in postmastectomy intensity-modulated radiation therapy.

This study reports a dosimetric comparison between treatment plans using static jaw and jaw tracking techniques in intensity-modulated radiation therapy (IMRT) for postmastectomy radiation therapy (PMRT). Seventeen patients treated for left-sided breast cancer with implant-based reconstruction were subjected to IMRT plans. Another group of 22 patients treated for left-sided breast cancer without reconstruction was also subjected to IMRT plans. The plans were generated using the Eclipse treatment planning system with static jaw and jaw tracking techniques. The dose-volume histograms and dosimetric indices, such as mean dose (Dmean), V20 Gy, V10 Gy, and V5 Gy (volumes receiving 20, 10, and 5 Gy at the least, respectively), and generalized equivalent uniform dose for organs at risk (OARs) were analyzed. A significant difference in the value of the dosimetric indices between the static jaw and jaw tracking plans was observed. For jaw tracking plans, the Dmean of the heart for the patients with implant-based reconstruction reduced from 11.6 ± 1.1 Gy to 10.0 ± 1.8 Gy, whereas the V5 Gy reduced from 92.0 ± 4.5% to 85.1 ± 8.4%. The Dmean of the heart for patients without reconstruction reduced from 11.0 ± 2.3 Gy to 9.8 ± 2.6 Gy, whereas the V5 Gy reduced from 81.4 ± 13.6% to 66.7 ± 17.4%. The dosimetric indices of OARs in the jaw tracking plans were significantly lower than those of the OARs in the static jaw plans. The jaw tracking technique was more effective for patients without reconstruction than for those with implant-based reconstruction.

Gold coated contact lens-type ocular in vivo dosimeter (CLOD) for monitoring of low dose in computed tomography: A Monte Carlo study.

PURPOSE: This study reports a sensitivity enhancement of gold-coated contact lens-type ocular in vivo dosimeters (CLODs) for low-dose measurements in computed tomography (CT). METHODS: Monte Carlo (MC) simulations were conducted to evaluate the dose enhancement from the gold (Au) layers on the CLODs. The human eye and CLODs were modeled, and the X-ray tube voltages were defined as 80, 120, and 140 kVp. The thickness of the Au layer attached to a CLOD ranged from 100 nm to 10 µm. The thickness of the active layer ranged from 20 to 140 µm. The dose ratio between the active layer of the Au-coated CLOD and a CLOD without a layer, i.e., the dose enhancement factor (DEF), was calculated. RESULTS: The DEFs of the first 20-µm thick active layer of the 5-µm thick Au-coated CLOD were 18.4, 19.7, 20.2 at 80, 120, and 140 kVp, respectively. The DEFs decreased as the thickness of the active layer increased. The DEFs of 100-nm to 5-µm thick Au layers increased from 1.7 to 5.4 for 120-kVp X-ray tube voltage when the thickness of the active layer was 140 µm. CONCLUSIONS: The MC results presented a higher sensitivity of Au-coated CLODs (∼20-times higher than that of CLODs without a gold layer). Au-coated CLODs can be applied to an evaluation of very low doses (a few cGy) delivered to patients during CT imaging.

Dose calculation of 3D printing lead shield covered by biocompatible silicone for electron beam therapy.

This study aims to calculate the dose delivered to the upstream surface of a biocompatible flexible absorber covering lead for electron beam treatment of skin and subcutaneous tumour lesions for head and neck. Silicone (Ecoflex™ 00-30, Smooth-On, Easton, PA, USA) was used to cover the lead to absorb backscattered electrons from lead. A 3D printer (Zortrax M300, Zortrax, Olsztyn, Poland) was used to fabricate the lead shield. Analytic calculation, simplified Monte Carlo (MC) simulation, and detailed MC simulation which includes a modeling of metal-oxide-semiconductor field-effect transistor (MOSFET) detector were performed to determine the electron backscatter factor (EBF) for 6 MeV and 9 MeV electron beams of a Varian iX Silhouette. MCNP6.2 was used to calculate the EBF and corresponding measurements were carried out by using MOSFET detectors. The EBF was experimentally measured by the ratio of dose at the upstream surface of the silicone to the same point without the presence of the lead shield. The results derived by all four methods agreed within 2.8% for 6 MeV and 3.4% for 9 MeV beams. In detailed MC simulations, for 6 MeV, dose to the surface of 7-mm-thick absorber was 103.7 [Formula: see text] 1.9% compared to dose maximum (Dmax) without lead. For 9 MeV, the dose to the surface of the 10-mm-thick absorber was 104.1 [Formula: see text] 2.1% compared to Dmax without lead. The simplified MC simulation was recommended for practical treatment planning due to its acceptable calculation accuracy and efficiency. The simplified MC simulation was completed within 20 min using parallel processing with 80 CPUs, while the detailed MC simulation required 40 h to be done. In this study, we outline the procedures to use the lead shield covered by silicone in clinical practice from fabrication to dose calculation.

Europium-Diethylenetriaminepentaacetic Acid Loaded Radioluminescence Liposome Nanoplatform for Effective Radioisotope-Mediated Photodynamic Therapy.

Photodynamic therapy (PDT) is an effective anticancer strategy with a higher selectivity and fewer adverse effects than conventional therapies; however, shallow tissue penetration depth of light has hampered the clinical utility of PDT. Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu3+ (Eu-DTPA)/photosensitizer (PS) loaded liposome (Eu/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective in vivo imaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, 64Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free 64Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). 64Cu-labeled Eu/VBBO lipo (64Cu-Eu/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID/g by enhanced permeability and retention effects, as revealed by in vivo positron emission tomography. Finally, the PDT using 64Cu-Eu/VBBO lipo demonstrated significantly higher in vitro and in vivo therapeutic effects than Cerenkov luminescence-induced PDT using 64Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.

Dynamic In Vivo X-ray Fluorescence Imaging of Gold in Living Mice Exposed to Gold Nanoparticles.

Dynamic in vivo biodistribution of gold nanoparticles (GNPs) in living mice was first successfully acquired by a pinhole X-ray fluorescence (XRF) imaging system using polychromatic X-rays. The system consisted of fan-beam X-rays to stimulate GNPs and a 2D cadmium zinc telluride (CZT) gamma camera to collect K-shell XRF photons emitted from the GNPs. 2D XRF images of kidney slices of three Balb/C mice were obtained within 2 minutes of irradiation per slice. 40 mg of GNPs suspended in a 0.2 mL phosphate-buffered saline was injected into the mice via a tail vein. The mice were scanned over a 60 min period after the injection of GNPs in order to acquire a dynamic biodistribution of GNPs. The concentrations of GNPs measured by the CZT gamma camera were then validated by inductively coupled plasma atomic emission spectroscopy and ex vivo L-shell XRF measurements using a silicon drift detector. The GNP concentrations in the right-side kidneys were 1.58% by weight (wt%) at T =0 min and 0.77 wt% at T=60 min after the injection. This investigation showed a dramatically reduced scan time and imaging dose. Hence, we conclude that dynamic in vivo XRF imaging of GNPs is technically feasible in a benchtop system. The developed pinhole XRF imaging system can be a potential molecular imaging modality for metal nanoparticles to emerge as a radiosensitizer and a drug-delivery agent.

Measuring radioenhancement by gold nanofilms: Comparison with analytical calculations.

PURPOSE: To measure radioenhancement by gold nanoparticles (GNPs) using gold nanofilms (GNFs). METHODS: GNFs of 20-100 nm thicknesses were prepared. The GNF attached to radiochromic film (RCF) was irradiated using 50, 220 kVp, and 6 MV X-rays. The radiation doses to the active layer of RCF with and without GNF were measured using an optical flatbed scanner and Raman spectrometer to estimate the dose enhancement factor (DEF). For verification, analytical calculations of DEF within the thickness of active layer and the ranges of secondary electrons were carried out. RESULTS: The DEFs for GNFs of 20 to 100 nm thicknesses measured by an optical scanner ranged from 2.1 to 6.1 at 50 kVp and 1.6 to 4.9 at 220 kVp. Similarly, the DEFs measured by Raman spectroscopy ranged from 2.6 to 4.6 at 50 kVp and 2.2 to 4.8 at 220 kVp. The calculated DEFs ranged from 1.5 to 3.6 at 50 kVp and from 1.7 to 4.7 at 220 kVp. Almost no dose enhancement was observed in 6 MV X-ray. The analytical DEFs seemed to be underestimated by averaging local enhancement over the entire active layer. However, analytical DEFs within the ranges of secondary electrons was much higher than the measured macroscopic DEFs. CONCLUSIONS: The experimental and analytical approaches developed in this study could quantitatively estimate radioenhancement by GNPs. Due to a short range of low-energy electrons emitted from gold, the microscopic radioenhancement within the ranges of low-energy electrons would be particularly important in a cell.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT). METHODS: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent. RESULTS: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%. CONCLUSIONS: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations.

Computational Modeling and Clonogenic Assay for Radioenhancement of Gold Nanoparticles Using 3D Live Cell Images.

Radioenhancement of gold nanoparticles (GNPs) has shown great potential for increasing the therapeutic efficiency of radiotherapy. Here we report on a computational model of radiation response, which was developed to predict the survival curves of breast cancer cells incubated with GNPs. The amount of GNP uptake was estimated using inductively coupled plasma-mass spectroscopy, and the three-dimensional (3D) intracellular distribution of GNPs was obtained using optical diffraction tomography. The developed computational model utilized the 3D live cell imaging and recent Monte Carlo techniques to calculate microscopic dose distributions within the cell. Clonogenic assays with and without GNPs were performed to estimate the radioenhancement for 150 kVp X rays in terms of cell survival fractions. Measured cell survival fractions were comparable with the computational model.

Pinhole X-ray fluorescence imaging of gadolinium and gold nanoparticles using polychromatic X-rays: a Monte Carlo study.

This work aims to develop a Monte Carlo (MC) model for pinhole K-shell X-ray fluorescence (XRF) imaging of metal nanoparticles using polychromatic X-rays. The MC model consisted of two-dimensional (2D) position-sensitive detectors and fan-beam X-rays used to stimulate the emission of XRF photons from gadolinium (Gd) or gold (Au) nanoparticles. Four cylindrical columns containing different concentrations of nanoparticles ranging from 0.01% to 0.09% by weight (wt%) were placed in a 5 cm diameter cylindrical water phantom. The images of the columns had detectable contrast-to-noise ratios (CNRs) of 5.7 and 4.3 for 0.01 wt% Gd and for 0.03 wt% Au, respectively. Higher concentrations of nanoparticles yielded higher CNR. For 1×1011 incident particles, the radiation dose to the phantom was 19.9 mGy for 110 kVp X-rays (Gd imaging) and 26.1 mGy for 140 kVp X-rays (Au imaging). The MC model of a pinhole XRF can acquire direct 2D slice images of the object without image reconstruction. The MC model demonstrated that the pinhole XRF imaging system could be a potential bioimaging modality for nanomedicine.

Evaluation of the microscopic dose enhancement for nanoparticle-enhanced Auger therapy.

The aim of this study is to investigate the dosimetric characteristics of nanoparticle-enhanced Auger therapy. Monte Carlo (MC) simulations were performed to assess electron energy spectra and dose enhancement distributions around a nanoparticle. In the simulations, two types of nanoparticle structures were considered: nanoshell and nanosphere, both of which were assumed to be made of one of five elements (Fe, Ag, Gd, Au, and Pt) in various sizes (2-100 nm). Auger-electron emitting radionuclides (I-125, In-111, and Tc-99m) were simulated within a nanoshell or on the surface of a nanosphere. For the most promising combination of Au and I-125, the maximum dose enhancement was up to 1.3 and 3.6 for the nanoshell and the nanosphere, respectively. The dose enhancement regions were restricted within 20-100 nm and 0-30 nm distances from the surface of Au nanoshell and nanosphere, respectively. The dose enhancement distributions varied with sizes of nanoparticles, nano-elements, and radionuclides and thus should be carefully taken into account for biological modeling. If the nanoparticles are accumulated in close proximity to the biological target, this new type of treatment can deliver an enhanced microscopic dose to the target (e.g. DNA). Therefore, we conclude that Auger therapy combined with nanoparticles could have the potential to provide a better therapeutic effect than conventional Auger therapy alone.