Variation in the relationship between odd isotopes of tin in mass-independent fractionation induced by the magnetic isotope effect.

Experimental results are presented showing the variation in the relationship between odd isotopes of tin (Sn) in mass-independent fractionation caused by the magnetic isotope effect (MIE), which has previously only been observed for mercury. These results are consistent with the trend predicted from the difference between the magnitudes of nuclear magnetic moments of odd isotopes with a nuclear spin. However, the correlation between odd isotopes in fractionation induced by the MIE for the reaction system used in this study (solvent extraction using a crown ether) was different from that reported for the photochemical reaction of methyltin. This difference between the two reaction systems is consistent with a theoretical prediction that the correlation between odd isotopes in fractionation induced by the MIE is controlled by the relationship between the spin conversion time and radical lifetime. The characteristic changes in the correlation between odd isotopes in fractionation induced by the MIE observed for Sn in this study provide a guideline for quantitatively determining fractionation patterns caused by the MIE for elements that have multiple isotopes with a nuclear spin. These results improve our understanding of the potential impact of the MIE on mass-independent fractionation observed in natural samples, such as meteorites, and analytical artifacts of high-precision isotope analysis for heavy elements.

Radiological imaging protection: a study on imaging dose used while planning computed tomography for external radiotherapy in Japan.

Previous studies have primarily focused on quality of imaging in radiotherapy planning computed tomography (RTCT), with few investigations on imaging doses. To our knowledge, this is the first study aimed to investigate the imaging dose in RTCT to determine baseline data for establishing national diagnostic reference levels (DRLs) in Japanese institutions. A survey questionnaire was sent to domestic RT institutions between 10 October and 16 December 2021. The questionnaire items were volume computed tomography dose index (CTDIvol), dose-length product (DLP), and acquisition parameters, including use of auto exposure image control (AEC) or image-improving reconstruction option (IIRO) for brain stereotactic irradiation (brain STI), head and neck (HN) intensity-modulated radiotherapy (IMRT), lung stereotactic body radiotherapy (lung SBRT), breast-conserving radiotherapy (breast RT), and prostate IMRT protocols. Details on the use of motion-management techniques for lung SBRT were collected. Consequently, we collected 328 responses. The 75th percentiles of CTDIvol were 92, 33, 86, 23, and 32 mGy and those of DLP were 2805, 1301, 2416, 930, and 1158 mGy·cm for brain STI, HN IMRT, lung SBRT, breast RT, and prostate IMRT, respectively. CTDIvol and DLP values in institutions that used AEC or IIRO were lower than those without use for almost all sites. The 75th percentiles of DLP in each treatment technique for lung SBRT were 2541, 2034, 2336, and 2730 mGy·cm for free breathing, breath holding, gating technique, and real-time tumor tracking technique, respectively. Our data will help in establishing DRLs for RTCT protocols, thus reducing imaging doses in Japan.

Historical changes of 236U/238U and 235U/238U isotopic ratios in Tokyo Bay from the 1960s to the 2000s.

We examine the historical changes of 236U/238U and 235U/238U in a sediment core collected in Tokyo Bay and elucidate the anthropogenic sources of uranium in the 1960s-2000s. Uranium-236 was detected in samples deposited in the 1960s-2000s, and the 236U/238U ratio of the sediment core shows peak values in the 1970s. The 235U/238U isotopic ratios in samples deposited in the early 1960s are almost identical to that of natural uranium, implying that the 236U might have originated from global fallout. A decrease in 235U/238U was observed in the late 1960s-2000s, suggesting that depleted uranium from nuclear fuel reprocessing increased the 236U/238U ratios in the sediment. The 236U/238U values in sediments from the 1980s-2000s were lower than those in the 1970s but considerably higher than those in the 1960s, suggesting that the main source of depleted uranium still remains around Tokyo Bay. Our results demonstrated that the depleted uranium released in the 1970s should be considered as an important end-member when using uranium isotopic ratios as environmental tracers in closed aquatic environments around industrial cities.

Temporal change of 236U/238U and 235U/238U isotopic ratios in atmospheric deposition in Tokyo and Akita from 1963 to 1979.

We examine the temporal changes of 236U/238U and 235U/238U in atmospheric deposition from samples collected in Tokyo and Akita from 1963 to 1979 and elucidate the spatial distribution and historical changes of the anthropogenic sources of uranium in Japan. The 236U/238U ratio of atmospheric deposition in Tokyo peaked in 1963 and again during the 1970s, while the corresponding 235U/238U ratios of atmospheric deposition during the second peak period were lower than that of natural uranium. The 236U/238U ratios of atmospheric deposition in Akita samples peaked in 1963. The 235U/238U ratios in Akita samples were almost identical to that of the natural uranium ratios. These results suggest that the peak of 236U/238U in 1963 corresponds to what is recognized as representative for global fallout. The increase of 236U/238U and the decrease of 235U/238U observed simultaneously in the 1970s indicate that depleted uranium has subsequently been released into the environment around Tokyo. The cumulative deposition density of 236U for atmospheric fallout samples collected in Tokyo from 1968 to 1979 is an order of magnitude larger than that of the global fallout, suggesting that the depleted uranium in the 1970s is a major component of 236U in Tokyo and should be considered as an end-member when using 236U as an environmental tracer in the industrial city. This knowledge can facilitate future research using 236U as an effective environmental tracer.

Monte Carlo study of dosimetric impact of gadolinium contrast medium in transverse field MR-Linac system.

The aim of this study is to evaluate the dosimetric impact of gadolinium contrast medium (Gadovist) in a transverse MR-Linac system using Monte Carlo methods. The dose distributions were calculated using two heterogeneous multi-layer phantoms consisting of Gadovist, water, bone, and lung. The photon beam was irradiated with a filed size of 5 × 5 cm2, and a transverse magnetic field of 0-3.0 T was applied perpendicular to the incident photon beam. Next, dose distributions for brain, head and neck (H&N), and lung cancer patients were calculated using a patient voxel-based phantom with and without replacing the patient's GTV with Gadovist. The dose at the water-Gadovist interface increased by 8% without a magnetic field. A similar dose increment was observed at 0.35 T. In contrast, the dose increment at the water-Gadovist interface was small at 1.5 T and a dose decrement of 5% was observed at 3.0 T. The dose variation at the lung-Gadovist interface was larger than that at the water-Gadovist interface. The mass collision stopping power ratio for Gadovist was 7% lower than that for water, whereas, the electron fluence spectra at the water-Gadovist interface increased by 17.5%. In a patient study, Gadovist increased the Dmean for brain, H&N, and lung cancer patients by 0.65-8.9%. The dose variation due to Gadovist grew large in the low-dose region in H&N and lung cancer. The GTV dose variation due to Gadovist in all treatment site was below 2% at 0-3 T if the Gadovist concentration was lower than 0.2 mmol/ml-1.

Impact of lung density on isolated lung tumor dose in VMAT using inline MR-Linac.

PURPOSE: This study investigated the impact of lung density on the isolated lung tumor dose for volumetric modulated arc therapy (VMAT) in an inline magnetic resonance linear accelerator (MR-Linac) using the Monte Carlo (MC) simulation. METHODS: CT images of the thorax phantoms with lung tumors of 1, 2, and 3 cm diameters were converted into voxel-base phantoms with lung densities of 0.1, 0.2, and 0.3 g/cm3, respectively. The dose distributions were calculated for partial-arc VMAT. The dose distributions were compared using dose differences, dose volume histograms, and dose volume indices. RESULTS: In all cases, the inline magnetic field significantly enhanced the lung tumor dose compared to that at 0 T. For the 1 cm lung tumor, the inline magnetic field of 1 T increased the minimum dose of 95% of the Planning target volume (PTV D95) by 14.0% in 0.1 g/cm3 lung density as compared to that in 0.3 g/cm3 at 0 T. In contrast, at 0 and 0.5 T, the PTV D95 in 0.3 g/cm3 lung density was larger than that in lung density of 0.1 g/cm3. For the 2 cm lung tumor, a similar tendency to 1 cm was observed, whereas the dose impact of lung density was smaller than that for 1 cm. For the 3 cm lung tumor, the lung tumor dose was independent of lung density at 0.5 T and 1.0 T. CONCLUSION: The inline MR-Linac with the magnetic field over 1 T can enhance the PTV D95 for VMAT regardless of the lung density.

Simultaneous determination of zircon U-Pb age and titanium concentration using LA-ICP-MS: Analysis data and crystallization temperature.

Simultaneous determination of zircon U-Pb age and titanium concentration for a single analysis spot gives both the crystallization age and temperature. In laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis, it is challenging to quantitatively analyse a low level of titanium concentration. Two approaches were employed using a quadrupole mass spectrometer equipped with a collision/reaction cell (CRC). In the first approach, the MS/MS mass-shift mode with oxygen reaction gas provided reliable and consistent measurement of titanium as 48Ti16O+. In the second approach, the titanium concentration was determined quantitatively from the signal intensity of 49Ti in the non-gas mode (without the inflow of collision/reaction gas into the CRC). The methods were applied to zircon samples of the Kurobegawa granite (KRG), the Okueyama granite (OKG), the Toki granite (TKG), and the Tono plutonic complex (TCP). The biotite K-Ar geochronology were employed for rock samples of the KRG, OKG, and TPC (N = 3) of which the zircon crystals were analysed. The obtained titanium concentrations of the zircon crystals can lead to the crystallization temperatures through Ti-in-zircon geothermometer.

Impact of the cavity on sinus wall dose in magnetic resonance image-guided radiation therapy.

PURPOSE: This study aims to investigate the impact of the cavity on the sinus wall dose by comparing dose distributions with and without the sinus under magnetic fields using Monte Carlo calculations. METHODS: A water phantom containing a sinus cavity (Empty) was created, and dose distributions were calculated for 1, 2, and 4 irradiation fields with 6 MV photons. The sinus in the phantom was then filled with water (Full), and the dose distributions were calculated again. The sinus was set to cubes of 2 cm and 4 cm. The magnetic field was applied to the transverse and inline direction under the magnetic flux densities of 0 T, 0.35 T, 0.5 T, 1.0 T, and 1.5 T. The dose distributions were analyzed by the dose difference, dose volume histogram, and D2 with sinus wall thicknesses of 1 and 5 mm. RESULTS: D2 in the "Empty" sinus wall under transverse magnetic fields for the 1-field and 4-field cases was 51.9% higher and 3.7% lower than that in the "Full" sinus wall at 1.5 T, respectively. Meanwhile, D2 in the Empty sinus wall under inline magnetic fields for 1-field and 4-fields was 2.3% and 2.6% lower than that in the "Full" sinus at B = 0 T, respectively, whereas D2 was 0.9% and 0.7% larger at 1.0 T, respectively. CONCLUSIONS: The impact of the cavity on the sinus wall dose depends on the magnetic flux density, direction of the magnetic field and irradiation beam, and number of irradiation fields.

Impact of transverse magnetic fields on dose response of a nanoDot OSLD in megavoltage photon beams.

PURPOSE: We investigated the impact of transverse magnetic fields on the dose response of a nanoDot optically stimulated luminescence dosimetry (OSLD) in megavoltage photon beams. METHODS: The nanoDot OSLD response was calculated via Monte Carlo (MC) simulations. The responses RQ and RQ,B without and with the transverse magnetic fields of 0.35-3 T were analyzed as a function of depth at a 10 cm × 10 cm field for 4-18 MV photons in a solid water phantom. All responses were determined based on comparisons with the response under the reference conditions (depth of 10 cm and a 10 cm × 10 cm field) for 6 MV without the magnetic field. In addition, the influence of air-gaps on the nanoDot response in the magnetic field was estimated according to Burlin's general cavity theory. RESULTS: The RQ as a function of depth for 4-18 MV ranged from 1.013 to 0.993, excepting the buildup region. The RQ,B increased from 2.8% to 1.5% at 1.5 T and decreased from 3.0% to 1.1% at 3 T in comparison with RQ as the photon energy increased. The depth dependence of RQ,B was less than 1%, excepting the buildup region. The top air-gap and the bottom air- gap were responsible for the response reduction and the response increase, respectively. CONCLUSIONS: The response RQ,B varied depending on the magnetic field intensity, and the variation of RQ,B reduced as the photon beam energy increased. The air-gaps affected the dose deposition in the magnetic fields.

Impact of transverse magnetic fields on dose response of a radiophotoluminescent glass dosimeter in megavoltage photon beams.

PURPOSE: The purpose of this study was to investigate the impact of transverse magnetic fields on the dose response of a radiophotoluminescent glass dosimeter (RGD) in megavoltage photon beams. METHODS: The RGD relative response (i.e., RGD dose per absorbed dose to water at the midpoint of the detector in the absence of the detector) was calculated using Monte Carlo (MC) simulations. Note that the Monte Carlo calculations do not account for changes of the signal production per unit dose to the RGD caused by the magnetic field strength. The relative energy response RQ , the relative magnetic response RB , and the relative overall response RQ , B with the transverse magnetic fields of 0-3 T were analyzed as a function of depth, for a 10 cm × 10 cm field in a solid water phantom, for 4-18 MV photons. Although magnetic resonance (MR) linacs with flattening filter free beams are commercially available, flattening filter beams were used to investigate the RGD response in this study. RQ is the response in beam quality Q relative to that in the reference beam with quality 6 MV, RB is the response in beam quality Q with the magnetic field relative to that in beam quality Q without the magnetic field, and the RQ,B is the response in beam quality Q with the magnetic field relative to that in the reference beam with quality 6 MV without the magnetic field. Two RGD orientations were considered: RGD long axis is parallel (direction A) and perpendicular (direction B) to the magnetic field. The reference irradiation conditions were at the depth of 10 cm for a 10 cm × 10 cm field for 6 MV, without the magnetic field. In addition, the influence of a small air-gap between the holder inner wall and the RGD on the dose response in the magnetic field, Rgap , was analyzed in detail. Rgap is the response in beam quality Q without/with the air-gap. RESULTS: RQ decreased by up to 2.7% as the energy increased in the range of 4-18 MV, except in the buildup region. In direction A, the variation of RB owing to the magnetic field strength was below 1.0%, regardless of the photon energy. In contrast, in direction B, RB decreased with increasing magnetic field strength and decreased up to 4.0% at 3 T for 10 MV. The Rgap for 0.03 and 0.05 cm air-gap models in direction A decreased up to 2.3% and up to 4.0%, respectively. CONCLUSIONS: The variation of RQ,B changed with the direction of the RGD relative to the magnetic field. For dose measurements, RGDs should be positioned with the long axis parallel to the magnetic field, without air-gaps.

Comparison of dose distributions between transverse magnetic fields of 0.35 T and 1.5 T for radiotherapy in lung tumor using Monte Carlo calculation.

We investigated the impact of the transverse magnetic fields of 0.35 T and 1.5 T on the dose distributions for a 6 MV beam, by using a thorax phantom with a lung tumor. First, the dose distributions in the magnetic flux densities of 0 T, 0.35 T, and 1.5 T were compared by increasing the number of irradiation fields. Next, the dose distributions for stereotactic body radiotherapy (SBRT) with 5-fields for an isolated lung tumor was compared in transverse magnetic fields. All dose distributions were calculated by the Monte Carlo method. The prescription doses for SBRT with 5-fields was 48 Gy for D95 (dose covering 95% volume) in the planning target volume (PTV). The dose distributions were analyzed by the dose difference map (DD map), dose volume histogram (DVH), and dose indices. For the 1-field, the dose distributions were more affected at 1.5 T rather than 0.35 T. The DVHs for PTV at 1.5 T almost agreed with those at 0 T for more than 5-fields. In contrast, the D98 in the PTV at 0.35 T reduced constantly by 6.0% with more than 5-fields. The D95 in PTV for SBRT with 5-fields was 9.0% lower at 0.35 T and 2.5% higher at 1.5 T, in comparison with that at 0 T. For dispersed irradiation angles of more than 5-fields, it is more desirable to use the magnetic flux density of 1.5 T than 0.35 T for the radiotherapy in the lung tumor.

Glandular dose indices using a glandular dose to air kerma volume histogram in mammography.

PURPOSE: To develop a dose evaluation for heterogeneous glandular dose distributions by using glandular dose indices obtained from a glandular dose to air kerma (GD/K) volume histogram in addition to the existing mean glandular dose (MGD) in mammography. METHODS: The mammographic x-ray fluence spectra were created using the EGSnrc/BEAMnrc Monte Carlo code. The combinations of the target and filter were Mo-Mo and W-Rh. The breast phantom was a half-ellipsoidal form, composed of adipose and glandular tissues, and a 1.5-mm-thick outer skin. The compressed breast thicknesses (CBT) were 2, 4, and 6 cm with a glandularity of 15%. Two types of breast voxel phantoms with homogeneous and realistic heterogeneous glandular distributions were modeled. The glandular dose distributions in both breast voxel phantoms were calculated using the simulated x-ray fluence spectra. The GD/K volume histograms for the glandular dose were presented by a relative glandular volume (%) as a function of the ratio of glandular dose (GD) and air kerma (K). Finally, the dose indices of MGD, GD2% /K (GD2% the dose covered by a 2% glandular volume), and VMGD (glandular volume percentage (%) receiving at least MGD), homogeneity index (HI) were obtained from the glandular dose distributions and GD/K volume histograms. The HI indicates the uniformity of GD distributions. RESULTS: The MGD in a standard heterogeneous phantom (CBT: 4 cm, glandularity: 15%) was 25%-37% lower than that in a standard homogeneous phantom. The lower the tube voltage, the larger was the difference between GD2% and MGD. The larger the CBT, the greater is the nonuniformity of the glandular dose distribution. The HI values for heterogeneous phantoms were higher than those for homogeneous phantoms. Values of VMGD were 35%-47% and increased slightly with the tube voltage. Values of VMGD for heterogeneous phantoms were smaller than those for homogenous phantoms at the same tube voltage. CONCLUSION: The GD distribution differs depending on the CBT and tube voltage, even if the MGD has the same value. The new GD indices proposed in this study are useful for the dose evaluation of the heterogeneous GD distributions.

Geant4 Monte Carlo investigation of the magnetic field effect on dose distributions in low-density regions in magnetic resonance image-guided radiation therapy.

It is necessary to evaluate the effect of the presence of a magnetic field when treating lung tumors with MRIgRT. In this study, the effect of transverse and longitudinal magnetic fields on dose distributions in low-density regions was quantitatively investigated. The dose distributions in a virtual lung phantom under the influence of magnetic fields were calculated using the Geant4 Monte Carlo code. The phantom size was 30 × 20 × 30 cm3, and it was composed of three layers: water (3 cm thickness), lung (12 cm thickness), and water (5 cm thickness). The density of the lung layer was set to 0.1, 0.3 and 0.6 g/cm3. The uniform magnetic flux densities of 0.35 T and 1.5 T were used for 2 × 2, 5 × 5, and 10 × 10 cm2 fields at a source-to-surface distance of 100 cm, using a 6 MV photon spectrum. The dose at the water-lung interface in a lung phantom increased by 58%, 51%, and 22% for the lung densities of 0.1, 0.3, and 0.6 g/cm3, respectively. In the 1.5 T longitudinal magnetic field, the penumbra at the lung center (at the depth of 9 cm) decreased by 5.14, 1.50 and 0.35 mm for a 5 × 5 cm2 field, respectively. The dose distributions in lowdensity regions are more affected by the magnetic field. In conclusion, the doses at the water-lung interface increased in the transverse magnetic field. The depth dose increased, and the penumbra decreased in the longitudinal magnetic field.

Response of a nanoDot OSLD system in megavoltage photon beams.

PURPOSE: The aim of this study was to investigate the response of a nanoDot optically stimulated luminescence dosimeter (OSLD) system in megavoltage photon beams. METHODS: The nanoDot response was compared with the ionization chamber measurements for 4-18-MV photons in a plastic water phantom. The response was also calculated by the Monte Carlo method. In addition, the perturbation correction factor, PQ, in the nanoDot cavity was calculated according to the Burlin's cavity theory. The angular dependence of the nanoDot was evaluated using a spherical phantom. RESULTS: The calculated and measured nanoDot responses at a 10-cm depth and 10 × 10-cm2 field were in agreement within 1% for 4-18-MV. The response increased by 3% at a 20 × 20-cm2 field for the lower energy of 4 MV; however, it was constant within ±1% for 6-18 MV. The response was in a range from 1.0 to 0.99 for mean photon energy of more than 1.0 MeV but it increased with less than the 1.0 MeV. PQ for the nanoDot cavity was approximately constant at 0.96-0.97 for greater than and equal to 10 MV. The angular dependence decreased by 5% and 3% for 6 and 15 MV, respectively. CONCLUSIONS: The nanoDot was energy-independent in megavoltage photon beams.

Impact of inline magnetic fields on dose distributions for VMAT in lung tumor.

The purpose of this study is to investigate the impact of inline magnetic field on dose distribution for volumetric modulated arc therapy (VMAT) in lung tumors located at the chest wall and mediastinum. Two VMAT plans for a thorax phantom with lung tumors of 1 cm and 2 cm in diameter located at the chest wall were created by a treatment planning system. Next, five clinical VMAT plans for a non-small cell lung cancer (NSCLC) at early stages I and II of 5 cm or less in diameter were also used. The planning target volume (PTV) sizes were in the range from 11.1 to 82.7 cm3. The prescription dose was 60 Gy for D95 in the PTV. The VMAT dose distributions without and with uniform inline magnetic field of 0.5 T and 1.0 T were calculated using the Monte Carlo method. The dose distributions were analyzed by dose volume histograms, dose differences, and dose indices. In all VMAT plans, the PTV dose was enhanced by inline magnetic field. The dose enhancement was larger with 1.0 T than with 0.5 T. In phantom plans, D98 in the PTV with 0.5 T and 1.0 T increased by 2.9-6.6 Gy and 3.9-9.8 Gy, respectively, in comparison with that at 0 T. Similarly, in clinical plans, it increased by 2.2-6.0 Gy and 3.9-10.7 Gy, respectively. Thus, the VMAT with the inline magnetic field was proved useful for the dose enhancement in the lung tumor located at the chest wall and mediastinum.

Perturbation effect of parallel-plate ionization chambers on buildup dose measurements in transverse magnetic fields.

The aim of this study is to investigate the perturbation effect of parallel-plate ionization chambers on the buildup dose measurement in transverse magnetic fields, using Monte Carlo (MC) simulation. The NACP-02 and ROOS parallel-plate chambers and a PTW31010 cylindrical chamber were modeled for buildup dose measurement in magnetic fields, using the EGSnrc/cavity code. The irradiation condition was set to a 10 × 10 cm2 field in a water phantom at a source-to-surface distance (SSD) of 100 cm, using 6-MV photon spectrum. Magnetic fields of 0 0.35, 1.0, 1.5, and 3.0 T were applied perpendicularly to the direction of the photon beam. The overall perturbation factor PQ,B for the ionization chambers in the magnetic fields was also calculated. The dose to water was enhanced with increasing the magnetic field strength at a depth of less than 1 cm. Over a depth of 1.5 cm, there was no significant difference in the depth doses with and without magnetic field in water. The maximum depth dose (%) for the NACP-02 and ROOS chambers at 1.5 T was higher up to 12% and 14% than the maximum depth dose at 0 T, respectively. The depth dose curves of a PTW31010 chamber have a similar tendency to those of water. The PQ,B values for each chamber were the largest at the phantom surface. The transverse magnetic field has a greater effect on the dose response of the NACP and ROOS chambers than that of the PTW31010 chamber in the buildup region.

Monte Carlo dose verification for a single-isocenter VMAT plan in multiple brain metastases.

The purpose of this study was to verify the accuracy of dose calculation algorithms of a treatment planning system for a single-isocenter volumetric modulated arc therapy (VMAT) plan in multiple brain metastases, by comparing the dose distributions of treatment planning system with those of Monte Carlo (MC) simulations. We used a multitarget phantom containing 9 acrylic balls with a diameter of 15.9 mm inside a Lucy phantom measuring 17 × 17 × 17 cm3. Seven VMAT plans were created using the multitarget phantom: 1 multitarget plan (MTP) and 6 single target plans (STP). Three of the STP plans had a large jaw field setting, almost equivalent to that of the MTP, while the other plans had a jaw field setting fitted to each planning target volume. The isocenter for all VMAT plans was set to the center of the phantom. The VMAT dose distributions were calculated using the analytical anisotropic algorithm (AAA) and were also recalculated through Acuros XB (AXB) and MC simulations under the same irradiation conditions. The AAA and AXB methods tended to overestimate dosage compared with the MC method in the MTP and in STPs with large jaw field settings. The dose distribution in single-isocenter VMAT plans for multiple brain metastases was influenced by jaw field settings. Finally, we concluded that MC-VMAT dose calculations are useful for 3D dose verification of single-isocenter VMAT plans for multiple brain metastases.

Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease characterized by joint destruction and loss of cartilage. There are many unmet needs in the treatment of OA and there are few promising candidates for disease-modifying OA drugs, particularly, anabolic agents. Here, we describe the identification of novel quinazolin-4(3 H)-one derivatives, which stimulate chondrocyte cartilage matrix production via TRPV4 and mitigate damaged articular cartilage. We successfully identified the water-soluble, highly potent quinazolin-4(3 H)-one derivative 36 and studied its intra-articular physicochemical profile to use in in vivo surgical OA model studies. Compound 36·HCl provided relief from OA damage in a rat medial meniscal tear (MT) model. Specifically, 36·HCl dose-dependently suppressed cartilage degradation and enhanced the messenger RNA expression of aggrecan and SOX9 in cartilage isolated from MT-operated rat knees compared with knees treated with vehicle. These results suggest that 36 induces anabolic changes in articular cartilage and consequently reduces OA progression.

Dependence of volume dose indices on dose calculation algorithms for VMAT-SBRT plans for peripheral lung tumor.

The purpose of this study was to investigate the dependence of volume dose indices on dose calculation algorithms for volumetric modulated arc therapy (VMAT) for stereotactic body radiotherapy (SBRT) plans to treat peripheral lung tumors by comparing them with those of Monte Carlo (MC) calculations. VMAT-SBRT plans for peripheral lung tumors were created using the Eclipse treatment planning system (TPS) for 24 patients with nonsmall cell lung cancer. VMAT dose distributions for gross tumor volume (GTV), internal target volume (ITV), and planning target volume (PTV) were calculated using the analytical anisotropic algorithm (AAA), the Acuros XB (AXB) algorithm, and a MC algorithm. VMAT dose distributions of the 3 algorithms were compared using their volume dose indices from dose volume histograms (DVHs), a dose difference map, and 3-dimensional gamma analysis. The DVHs for GTV and ITV from AAA, AXB, and MC were in good agreement. The difference between the ITV and PTV volume dose indices from AAA and MC increased as D98, D95, D80, D50, and D2. In particular, the difference between D98 for PTV from AAA and MC was up to 48%. A >5% difference between D95 for PTV from AAA and MC was 11 patients, but only 2 patients for ITV. The volume dose indices for AXB were near those of MC. AAA tended to overestimate the PTV volume dose indices compared to AXB and MC. Thus, we propose that the volume dose indices for the ITV be used because they are independent of dose calculation algorithms.