Time-resolved dosimetry with pencil-beam scanning for quality assurance/quality control in particle therapy.

This study aimed to measure dose in a scanning carbon beam-irradiation field with high sampling rate that is sufficient for identifying spots and verifying the characteristics of the scanning beam that cannot generally be derived from the dose. To identify the spot, which is the smallest control unit of beam information during irradiation, effecting measurements with a sampling time of 10 µs or shorter is necessary. The provided dose within a specific time is referred to as time-resolved dose (TRD). We designed a circuit for time-resolved dosimetry using a fast-data acquisition unit (SL1000, Yokogawa Electric Co.), which can measure 100 000 samples per second. Moreover, we used converters to enable a connection between an ionization chamber (IC) and the SL1000. TRD was measured successfully using point irradiation and two-dimensional irradiation patterns in a scanned carbon beam. Based on the moving time of the spot obtained from the position monitor, the dose delivered to the IC from each spot position (spot dose) was interpreted. The spot dose, displacement of the chamber from the beam's center axis, and beam size were derived using TRD and position monitor outputs, which were measured concurrent with TRD. Spot dose up to a radius of 8 mm area from the IC's center were observed. Using the spot-dose equations and simulation, we show that the spot dose of each position varies depending on the beam size and displacement of the IC's center from the beam's center axis. We devise an interpretation method for the characteristics that may apply to quality assurance, such as the verification of the trend for the beam axis and isocenter to coincide, as well as beam-size verification.

Feasibility study of using Stereotactic Field Diode for field output factors measurement and evaluating three new detectors for small field relative dosimetry of 6 and 10 MV photon beams.

This study assesses the feasibility of using stereotactic field diode (SFD) as an alternate to gaf chromic films for field output factor (FF) measurement and further evaluating three new detectors for small field dosimetry. Varian 21EX linear accelerator was used to generate 6 and 10 MV beams of nominal square fields ranging from 0.5 × 0.5 cm2 to 10 × 10 cm2 . One passive (EBT3 films) and five active detectors including IBA RAZOR diode(RD), SFD, RAZOR nanochamber (RNC), pinpoint chamber (PTW31023), and semiflex chamber (PTW31010) were employed. FFs were measured using films and SFD while beam profiles and percentage depth dose (PDD) distribution were acquired with active detectors. Polarity (kpol ) and recombination (ks ) effects of ion chambers were determined and corrected for output ratio measurement. Correction factors (CF) of RD, RNC, and PTW31023 in axial and radial orientation were also measured. Stereotactic field diode measured FFs have shown good agreement with films (with difference of <1%). RD and RNC measured beam profiles were within 3% deviation from the SFD values. Variation in kpol with field size for RNC and PTW31023 was up to 4% and 0.4% (for fields ≥ 1 × 1 cm2 ), respectively, while variation in ks of PTW31023 was <0.2 %. The maximum values of CF have been calculated to be 5.2%, 2.0%, 13.6%, and 25.5% for RD, RNC, PTW31023-axial, and PTW31023-radial respectively. This study concludes that SFD with appropriate CFs as given in TRS 483 may be used for measuring FFs as an alternate to EBT3 films. Whereas RD and RNC may be used for beam profile and PDD measurement in small fields. Considering the limit of usability of 2%, RNC may be used without CF for FF measurement in the smallfields investigated in this study.

Commissioning of a respiratory gating system involving a pressure sensor in carbon-ion scanning radiotherapy.

This study reports the commissioning methodology and results of a respiratory gating system [AZ - 733 V/733 VI (Anzai Medical Co., Japan)] using a pressure sensor in carbon-ion scanning radiotherapy. Commissioning includes choosing a location and method for pressure sensor installation, delay time measurement of the system, and the final flow test. Additionally, we proposed a methodology for the determination of a threshold level of generating an on/off gate for the beam to the respiratory waveform, which is important for clinical application. Regarding the location and method for installation of the pressure sensor, the actual person's abdomen, back of the body position, and supine/prone positioning were checked. By comparing the motion between the pressure sensor output and the reference LED sensor motion, the chest rear surface was shown to be unsuitable for the sensor installation, due to noise in the signal caused by the cardiac beat. Regarding delay time measurement of the system, measurements were performed for the following four steps: (a). Actual motion to wave signal generation; (b). Wave signal to gate signal generation; (c). Gate signal to beam on/off signal generation; (d). Beam on/off signal to the beam irradiation. The total delay time measured was 46 ms (beam on)/33 ms (beam off); these were within the prescribed tolerance time (<100 ms). Regarding the final flow test, an end-to-end test was performed with a patient verification system using an actual carbon-ion beam; the respiratory gating irradiation was successfully performed, in accordance with the intended timing. Finally, regarding the method for determining the threshold level of the gate generation of the respiration waveform, the target motion obtained from 4D-CT was assumed to be correlated with the waveform obtained from the pressure sensor; it was used to determine the threshold value in amplitude direction.

End-to-end dosimetry audit for three-dimensional image-guided brachytherapy for cervical cancer.

BACKGROUND: End-to-end dosimetry audit for brachytherapy is challenging due to the steep dose gradient. However, it is an efficient method to detect unintended errors in actual clinical practice. PURPOSE: We aimed to develop an on-site end-to-end test phantom for three-dimensional image-guided brachytherapy (IGBT) for cervical cancer. METHODS: The test phantom we developed consisted of a water tank with an applicator/detector holder. The holder was designed to accommodate the applicator and insert an ionization chamber (PinPoint; PTW, Freiburg, Germany) to measure the dose at point A. Imaging and reconstruction were performed in the same way as performed for a patient. The feasibility of our test phantom was assessed in two different hospitals using tandem and ovoid (made of either metal or carbon) applicators that the hospitals provided. RESULTS: The measured and calculated doses at point A were compared for each applicator. We observed that the values obtained using metal applicators were consistently lower, on an average by -2.3%, than the calculated values, while those obtained using carbon applicators were comparable to the calculated values. This difference can be attributed to the attenuation of the dose by the metal applicators, resulting in a lower dose at point A. The majority of treatment planning system, including the one used in this study, do not account for the material of applicator. CONCLUSIONS: An end-to-end test phantom for IGBT was developed, tested, and applied in a dosimetry audit in hospitals and showed favorable results for evaluating the point A dose.

Monte Carlo-calculated beam quality and perturbation correction factors validated against experiments for Farmer and Markus type ionization chambers in therapeutic carbon-ion beams.

Objective. In current dosimetry protocols, the estimated uncertainty of the measured absorbed dose to waterDwin carbon-ion beams is approximately 3%. This large uncertainty is mainly contributed by the standard uncertainty of the beam quality correction factorkQ. In this study, thekQvalues in four cylindrical chambers and two plane-parallel chambers were calculated using Monte Carlo (MC) simulations in the plateau region. The chamber-specific perturbation correction factorPof each chamber was also determined through MC simulations.Approach.kQfor each chamber was calculated using MC code Geant4. The simulatedkQratios in subjected chambers and reference chambers were validated through comparisons against our measured values. In the measurements in Heavy-Ion Medical Accelerator in Chiba,kQratios were obtained fromDwvalues of60Co, 290- and 400 MeV u-1carbon-ion beams that were measured with the subjected ionization chamber and the reference chamber. In the simulations,fQ(the product of the water-to-air stopping power ratio andP) was acquired fromDwand the absorbed dose to air calculated in the sensitive volume of each chamber.kQvalues were then calculated from the simulatedfQand the literature-extractedWairand compared with previous publications.Main results. The calculatedkQratios in the subjected chambers to the reference chamber agreed well with the measuredkQratios. ThekQuncertainty was reduced from the current recommendation of approximately 3% to 1.7%. ThePvalues were close to unity in the cylindrical chambers and nearly 1% above unity in the plane-parallel chambers.Significance. ThekQvalues of carbon-ion beams were accurately calculated in MC simulations and thekQratios were validated through ionization chamber measurements. The results indicate a need for updating the current recommendations, which assume a constantPof unity in carbon-ion beams, to recommendations that consider chamber-induced differences.

Radio-fluorogenic nanoclay gel dosimeters with reduced linear energy transfer dependence for carbon-ion beam radiotherapy.

PURPOSE: The precise assessment of the dose distribution of high linear energy transfer (LET) radiation remains a challenge, because the signal of most dosimeters will be saturated due to the high ionization density. Such measurements are particularly important for heavy-ion beam cancer therapy. On this basis, the present work examined the high LET effect associated with three-dimensional gel dosimetry based on radiation-induced chemical reactions. The purpose of this study was to create an ion beam radio-fluorogenic gel dosimeter with a reduced effect of LET. METHODS: Nanoclay radio-fluorogenic gel (NC-RFG) dosimeters were prepared, typically containing 100 µM dihydrorhodamine 123 (DHR123) and 2.0 wt% nanoclay together with catalytic additives promoting Fenton or Fenton-like reactions. The radiological properties of NC-RFG dosimeters having different compositions in response to a carbon-ion beam were investigated using a fluorescence gel scanner. RESULTS: An NC-RFG dosimeter capable of generating a fluorescence intensity distribution reflecting the carbon-ion beam dose profile was obtained. It was clarified that the reduction of the unfavorable LET dependence results from an acceleration of the reactions between DHR123 and H2 O2 , which is a molecular radiolysis product. The effects of varying the preparation conditions on the radiological properties of these gels were also examined. The optimum H2 O2 catalyst was determined to include 1 mM Fe3+ ions, and the addition of 100 mM pyridine was also found to increase the sensitivity. CONCLUSIONS: This technique allows the first-ever evaluation of the depth-dose profile of a carbon-ion beam at typical therapeutic levels of several Gy without LET effect.

Regulation of gene expression in retrovirus vectors by X-ray and proton beam radiation with artificially constructed promoters.

BACKGROUND: We previously obtained an X-ray responsive promoter from 11 promoters that we constructed. In the present study, we aimed to determine the efficiency of our promoter construction method. In addition, the reactivity of the promoter to X-rays in vivo is also investigated. METHODS: Promoters constructed by linking the TATA box to randomly combined binding sequences of transcription factors activated by radiation were cloned to prepare a promoter library. Combinations of promoters and various genes were stably-transfected into HeLa cells to establish recombinant cell lines, which were then exposed to X-rays or a proton beam to observe gene expression enhancement with or without anti-oxidants. Tumors of luciferase-expressing recombinant cells on mice were exposed to X-rays and promoter activation was evaluated by detecting bioluminescence. As a model for in vitro suicide gene therapy, fcy::fur-expressing recombinant cells were exposed to X-rays before incubation with 5-fluorocytosin. Cell viability was determined with WST-8. RESULTS: Twenty-five of the 62 promoters in the library enhanced luciferase activity over five-fold, 6 h after receiving 10 Gy of X-ray irradiation, suggesting the effectiveness of our method. Luciferase activity in recombinant cells was enhanced by X-rays and, to a lesser extent, by a proton beam. Anti-oxidants attenuated the enhancement, suggesting the involvement of oxidative stress. Promoters were less reactive to X-rays in tumors on mice. In our suicide gene therapy model, survival of post-irradiated cells decreased dose-dependently with 5-fluorocytosin. CONCLUSIONS: Our method was efficient in generating radiation responsive promoters. Furthermore, we have successfully shown a potential therapeutic use for one of these promoters.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.

PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

Computational modeling for the evaluation of suppressed scintillation yields in plastic scintillators using Geant4.

The yield of scintillation photons emitted from scintillators is considered to be proportional to the LET (linear energy transfer) which is energy distribution per unit length, in the low-LET domain, but not proportional in the high LET domain due to the suppression yield from the so-called quenching effect. Ogawa et al. proposed a computational method to estimate scintillation yield using Monte Carlo simulations considering the principle of the FRET (fluorescence resonance energy transfer) process, which is a phenomenon of energy transfer between fluorescent molecules. In their study, the track structure simulations could reproduce measured yields of scintillation. However, Ogawa et al.'s model was not suitable for estimating the scintillation yields when the particle energy was low when using condensed history simulations. Therefore, we propose a new method for estimating scintillation yields more accurately using Geant4 to improve the model calculations based on condensed history simulations. We simulated the local energy deposition pattern in a NE102A plastic scintillator to calculate the number of excitors in the microscopic volume for various nuclides (helium to argon ions). The suppressed scintillation yields were estimated using the model calculations of sequential FRET processes while considering the inactivation of the excitors selected as donors of the FRET process. The model calculations successfully reproduced the experimental scintillation yields within 10% error for the lighter ions up to neon. However, when the analysis was repeated for silicon and argon, the maximum error in the scintillation yields increased up to 27%. The proposed computational model for the evaluation of the suppressed scintillation yields emitted from NE102A scintillator irradiated with heavy ions using sequential FRET calculations with condensed history method returned simulated scintillation yields.

Dose response of a radiophotoluminescent glass dosimeter for TomoTherapy, CyberKnife, and flattening-filter-free linear accelerator output measurements in dosimetry audit.

PURPOSE: We experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan. METHODS: A custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm. RESULTS: The correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions. CONCLUSION: RPLD can be successfully used as a dosimetry audit tool for modern treatment units.

Whole Three-Dimensional Dosimetry of Carbon Ion Beams with an MRI-Based Nanocomposite Fricke Gel Dosimeter Using Rapid T1 Mapping Method.

MRI-based gel dosimeters are attractive systems for the evaluation of complex dose distributions in radiotherapy. In particular, the nanocomposite Fricke gel dosimeter is one among a few dosimeters capable of accurately evaluating the dose distribution of heavy ion beams. In contrast, reduction of the scanning time is a challenging issue for the acquisition of three-dimensional volume data. In this study, we investigated a three-dimensional dose distribution measurement method for heavy ion beams using variable flip angle (VFA), which is expected to significantly reduce the MRI scanning time. Our findings clarified that the whole three-dimensional dose distribution could be evaluated within the conventional imaging time (20 min) and quality of one cross-section.

Performance of the NIRS fast scanning system for heavy-ion radiotherapy.

PURPOSE: A project to construct a new treatment facility, as an extension of the existing HIMAC facility, has been initiated for the further development of carbon-ion therapy at NIRS. This new treatment facility is equipped with a 3D irradiation system with pencil-beam scanning. The challenge of this project is to realize treatment of a moving target by scanning irradiation. To achieve fast rescanning within an acceptable irradiation time, the authors developed a fast scanning system. METHODS: In order to verify the validity of the design and to demonstrate the performance of the fast scanning prior to use in the new treatment facility, a new scanning-irradiation system was developed and installed into the existing HIMAC physics-experiment course. The authors made strong efforts to develop (1) the fast scanning magnet and its power supply, (2) the high-speed control system, and (3) the beam monitoring. The performance of the system including 3D dose conformation was tested by using the carbon beam from the HIMAC accelerator. RESULTS: The performance of the fast scanning system was verified by beam tests. Precision of the scanned beam position was less than +/-0.5 mm. By cooperating with the planning software, the authors verified the homogeneity of the delivered field within +/-3% for the 3D delivery. This system took only 20 s to deliver the physical dose of 1 Gy to a spherical target having a diameter of 60 mm with eight rescans. In this test, the average of the spot-staying time was considerably reduced to 154 micros, while the minimum staying time was 30 micros. CONCLUSIONS: As a result of this study, the authors verified that the new scanning delivery system can produce an accurate 3D dose distribution for the target volume in combination with the planning software.

A clinical study of curative partial breast irradiation for stage I breast cancer using carbon ion radiotherapy.

BACKGROUND AND PURPOSE: Our institute initiated carbon ion radiotherapy research for patients with stage I breast cancer in April 2013. The purpose of this article is to evaluate the treatment outcome of cases treated outside clinical trial up to May 2020. MATERIALS AND METHODS: Eligibility criteria of the patients were having untreated stage I breast cancer and being unsuitable for operation for physical or mental reasons. The irradiated volume was defined as the gross tumor including intraductal components. The dose escalation study was initially conducted four times a week for a total of 52.8 Gy [relative biological efficacy (RBE)]. After confirming that adverse effects were within acceptable range, the total dose was increased to 60.0 Gy (RBE). RESULTS: Between April 2013 and November 2015, 14 cases were treated. The median follow up period was 61 months. No adverse toxicities were observed except for grade 1 acute skin reaction in 10 cases. The time required from carbonion radiotherapy to tumor disappearance was 3 months in 1 case, 6 months in 3 cases, 12 months in 4 cases, and 24 months in 5 cases. The third case developed local recurrence 6 months after radiotherapy. Twelve patients with luminal subtype received 5-year endocrine therapy. Thirteen of 14 tumors have been maintaining complete response with excellent cosmetic results. CONCLUSIONS: The time from carbon ion radiotherapy to tumor disappearance was longer than expected, but complete tumor disappearance was observed except for one high-grade case. With careful patient selection, carbonion radiotherapy in patients with stage I breast cancer is deemed effective and safe, and further research is recommended.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries.

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2-6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9-105.9), 77.7 Gy EQD2 (range, 56.9-99.1), 68.0 Gy EQD2 (range, 48.6-90.7) and 62.0 Gy EQD2 (range, 39.6-83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

A Phase I clinical trial of carbon ion radiotherapy for Stage I breast cancer: clinical and pathological evaluation.

Even with its high RBE and >20 years history, there had been no breast cancer clinical trial using carbon-ion radiotherapy. We started a Phase I trial of carbon ion radiotherapy for Stage I breast cancer in 2013. This article describes the clinical and pathological evaluation of this study. Patients with low-risk Stage I breast cancer were eligible. A dose escalation study was designed, with dose levels of 48.0, 52.8 or 60.0 Gy relative biological effectiveness (RBE) administered in four fractions within 1 week. Three months after radiotherapy, the patients underwent tumor excision for pathological evaluation. Between April 2013 and December 2014, three cases receiving 48 Gy (RBE), three cases receiving 52.8 Gy (RBE) and one case receiving 60 Gy (RBE) underwent this protocol. No adverse effects were observed except for Grade 1 acute skin reaction in four cases. Pathological evaluation revealed that all four cases with doses of 52.8 Gy (RBE) and 60.0 Gy (RBE) achieved Grade 2b or more, but only two cases reached Grade 3. At the end of 2017, all cases were alive without recurrence or late had not caused any late adverse reaction. Carbon ion radiotherapy for Stage I breast cancer seems to be safe, and we found that it did not reach enough treatment effect 3 months after the treatment.

Comparison of passive and scanning irradiation methods for carbon-ion radiotherapy for breast cancer.

The dose distribution of passive and scanning irradiation for carbon-ion radiotherapy for breast cancer was compared in order to determine the preferred treatment method. Eleven Japanese patients who received carbon-ion radiotherapy for breast cancer were retrospectively analyzed. The original clinical plans were used for the passive irradiation method, while the plans for the scanning irradiation method were more recently made. Statistical analysis suggested that there was no significant difference in superiority in terms of dose distribution between the passive and scanning irradiation methods. The present study found that the scanning irradiation method was not always superior to the passive method, despite a previous study having reported the superiority of scanning irradiation. The present result is considered to arise from characteristics of breast cancer treatment, such as the simplicity of the organ at risk and the shallow depth point of the target from the skin. It is noteworthy that the present study suggests that the passive irradiation method can provide better dose distribution, depending on the case.

Construction of strong mammalian promoters by random cis-acting element elongation.

Synthetic oligonucleotides containing one of four kinds of cis-acting elements, binding sites for activating protein-1 (AP-1), nuclear factor kappaB (NF-kappaB), CArG binding factor A (CBF-A), and nuclear factor Y (NF-Y), were randomly ligated to construct DNA fragments. These fragments were inserted into the SalI site of a promoter probe vector; pGL3-TATASal, which is located immediately upstream of the TATA box sequence of the human heme oxygenase 1 gene and linked to the luciferase gene to construct 11 plasmid vectors. When these vectors were introduced into PC-3 cells of human prostate cancer, 6 out of the 11 transfectants showed a significantly higher luciferase activity than pGL3-TATASal. The two strongest promoters (clone 6 and clone 11) were investigated further Clone 6 turned out to be the strongest, showing a 3.0- and 8.4-fold activity in comparison to the two frequently used promoters--the cytomegalovirus (CMV) immediate early promoter and the simian virus 40 (SV40) early promoter respectively. Clone 11 was less active than clone 6, but still showed higher activity than the two promoters. When the plasmids were introduced into nine other cell lines, their activities varied but were still comparable to the two promoters. These results indicate that the method used here is simple and efficient for constructing strong promoters that are potentially useful for vectors in either gene therapy or recombinant vaccine.

Organic-Gelatin-Free Nanocomposite Fricke Gel Dosimeter.

We report a nanocomposite Fricke gel (NC-FG) dosimeter prepared using only Fe2+ and nanoclay in water, without any organic gelling agents. This dosimeter gels due to its thixotropic properties and exhibits linear energy transfer (LET)-independent radiological properties under carbon ion beam irradiation. The radiation sensitivity of this dosimeter was 1.8 [s-1 kGy-1], which is three times higher than that reported previously (0.6 [s-1 kGy-1]) for a similar dosimeter containing gelatin. The Fe3+ yield was determined to be 0.19 µmol/J by evaluating the difference in spin-lattice relaxivity between Fe3+ and Fe2+. A further increase in the radiation sensitivity was observed upon addition of the hydrated electron scavenger N2O, suggesting the reduction of Fe3+ by a hydrated electron. LET-dependent variations of the contributions of OH radicals and hydrated electrons compensate each other in the oxidation yield of NC-FG. This is the main mechanism of the suppression of LET effects in the Bragg peak compared to conventional Fricke dosimeters. The radiation-induced oxidation yield G(Fe3+) can be described by the stoichiometric equation {G(Fe3+) = G(OH) - G(eaq-) + 2G(H2O2) + G(H)} with the reported LET dependence of the primary yield of water decomposition radicals. The calculated results are in approximate agreement with the absolute value of the experimental oxidation yield of NC-FG. The effects of the addition of small amounts of radical scavengers (nitrate, selenate, or cadmium) are also evaluated. The sensitivity was divided into two types, and influences of intermediate radicals after scavenging reaction are indicated.