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The distinguishing feature and current technique progress of tumor treatment with heavy-ion beams is introduced in the paper. Additional superiority to tumor treatment from a radioactive ion beam (RIB) is emphatically discussed. The experimental research of the radioactive 9C-ion beams aimed at tumor treatment at Heavy Ion Medical Accelerator in Chiba (HIMAC), National Institute of Radiological Sciences (NIRS), Japan is described in detail, including production of the beams, optimization of parameters, distribution of depth dose, survival effect of cell and comparison of RBE between 9C- and 12C-beams. Results show that under 40 mm thick Beryllium target and 10 mm thick aluminum degrader at full (5%) momentum acceptance, the production rate and purity of the produced 9C-beams are 9.07⊗10-6 and 82.88% respectively with the primary 12C-beams of 430 MeV/u and 1.8⊗109 pps. A uniform irradiation field with homogeneity up to 89.6% inside central area 10 mm in diameter is obtained by using spot scanning. In this case, the dose rate at the entrance is 0.5 Gy/h. In survival experiment of cells, the average relative biological effectiveness (RBE) of 9C-beams is 5.28 and 2.93 for 12C-beams in the region around Bragg peak. The RBE of 9C-beams is 1.8 times higher than that of 12C-beams. It indicates that cell-killing efficiency of 9C-beams is stronger than that of 12C-beams. 9C-beams are more efficacious for tumor treatment than 12C-beams. [ABSTRACT FROM AUTHOR]

Abstract: For the effective utilization of the favorable properties of heavy-ion beams in cancer treatment, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient''s body. For this purpose, the utilization of positron emitters induced in therapeutic irradiation is, at present, the only feasible method for in situ and non-invasive monitoring of heavy-ion therapy. In this study, we performed irradiation experiments with three species of ions to a water target, and the annihilation gamma-ray distributions were obtained with a positron camera. We applied the maximum likelihood estimation (MLE) method for the detected distributions to derive the range of incident ions and the deposited dose distribution in the target. As a result, the ranges were determined with a difference between the MLE range R MLE and the experimental range R exp less than 1.1mm. The good agreement between the estimated dose distribution with the MLE method and the measured one implies that a deposited dose distribution in a target could be estimated from a detected annihilation gamma-ray distribution. [Copyright &y& Elsevier]

Abstract: To explore the potential of double irradiation source, radioactive 9C-ion beam, in tumor therapy, a comparative study on the surviving effect of human salivary gland cells at different penetration depths between 9C and 12C-ion beams has been carried out. The 9C-ion beam came out more efficient in cell killing at the depths around its Bragg peak than the 12C beam, especially at the distal side of the Bragg peak. Compared to the 12C beam, an increase in RBE by a factor of up to 2.13 has been observed at the depths distal to the Bragg peak of the 9C beam. The 9C beam showed an enhanced biological effect at the penetration depths around its Bragg peak, corresponding to the stopping region of the incident 9C-ions and where the delayed low-energy particles were emitted. Further analysis revealed that cell lethality by the emitted particles from the stopping 9C-ions is responsible for the excessive biological effect at the penetration depths around the Bragg peak of the 9C beam. [Copyright &y& Elsevier]

The emitted particles from a β-delayed particle decay beam must enhance biological effects in the region of interest and such a radioactive ion beam may be useful in cancer treatment. To test this therapeutic purpose of β-delayed particle decay beams, 9C beams were produced in the secondary beam line at HIMAC for the first time. The thickness of production target and degrader to yield a 9C beam with higher production rate and purity was optimized and the momentum distribution of the produced 9C beam under the optimal condition was measured. For upcoming radiobiological experiments, a uniform irradiation field for the produced 9C beam was made by means of wobbling magnets. [Copyright &y& Elsevier]

Due to the favorable characteristics of heavy-ion beams such as dose localization as well as high relative biological effectiveness, heavy-ion cancer therapy is attracting growing interests all over the world. The application of β-delayed particle decay beams like 9C ions in cancer therapy is expected to further improve the treatment efficacy of the modality of heavy-ions. For the first time 9C beams were produced in the secondary beam line (SBL) of the HIMAC facility with a primary 12C beam of 430 MeV/n. The production conditions providing a 9C beam with higher production rate and purity were optimized using different thick production targets and degraders. The results show setting the momentum acceptance to the full value of 5% the production rate is 9.07 × 10−6 and the purity is 82.88% for the produced 9C beam under the optimal condition. Because of the large momentum spread for a secondary beam, the momentum distribution of the produced 9C beam at the optimal condition was measured. The momentum among the beam had a nearly Gaussian profile with a standard deviation of 26.1 MeV/c/n and the largest component of the momenta appeared around 838.9 MeV/c/n. In order to form a relatively large uniform irradiation field being appropriate to further biological experiments for the produced 9C beam, the scanning magnets in the irradiation system of the SBL, operating in a wobbling mode, was used. A uniform irradiation field of 20 mm in diameter could be achieved with homogeneity of 93.8%. The work presented in this paper provides a substantial basis for the further studies with 9C beams for the therapeutic purpose. [Copyright &y& Elsevier]

Particle radiotherapy using proton and heavy ion beams has shown improved clinical results and is a promising cancer therapy which is expected to gradually spread in Japan. There are, however, no special regulations for radiotherapy treatment facilities. They have been operated under the same safety regulations as for a research facility using a research accelerator. Significantly high-energy radiation is necessary for particle radiotherapy compared with conventional radiation therapy. The treatment facility, therefore, should have a large accelerator, which is installed in a room with a thick shield wall. Data on radiation protection for such high energy medical facilities is fragmentary and insufficient. In this study, we examined the necessity of other regulations for the safe operation of medical facilities for particle radiotherapy. First, we measured activation levels of the therapeutic devices and of patients. Next the safety level of the medical facility was evaluated from the viewpoint of radiation protection. We have confirmed the facilities can be safely operated by present regulations given in the Law Concerning Prevention from Radiation Hazards due to Radiation Isotopes, etc. or the Law for Health Protection and Medical Care.

In proton therapy, it is important to evaluate the field irradiated with protons and the deposited dose distribution in a patient's body. Positron emitters generated through fragmentation reactions of target nuclei can be used for this purpose. By detecting the annihilation gamma rays from the positron emitters, the annihilation gamma ray distribution can be obtained which has information about the quantities essential to proton therapy. In this study, we performed irradiation experiments with mono-energetic proton beams of 160 MeV and the spread-out Bragg peak beams to three kinds of targets. The annihilation events were detected with a positron camera for 500 s after the irradiation and the annihilation gamma ray distributions were obtained. In order to evaluate the range and the position of distal and proximal edges of the SOBP, the maximum likelihood estimation (MLE) method was applied to the detected distributions. The evaluated values with the MLE method were compared with those estimated from the measured dose distributions. As a result, the ranges were determined with the difference between the MLE range and the experimental range less than 1.0 mm for all targets. For the SOBP beams, the positions of distal edges were determined with the difference less than 1.0 mm. On the other hand, the difference amounted to 7.9 mm for proximal edges.

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

Purpose: To evaluate the potential importance of radioactive 9C-ion beam in cancer radiotherapy., Methods and Materials: Human salivary gland (HSG) cells were exposed to a double-radiation-source 9C beam at different depths around the Bragg peak. Cell survival fraction was determined by standard clonogenic assay. For comparison, the same experiment was conducted for a therapeutic 12C beam. To determine relative biologic effectiveness (RBE) values, HSG cells were also irradiated with 60Co gamma-rays of fractionation scheme as the reference., Results: The 9C beam was more efficient in cell killing at the depths around its Bragg peak than was the 12C beam, which corresponded to the 9C-ion stopping region and where delayed low-energy particles were emitted. The RBE value at 50% survival level for the 9C beam varied from 1.38 to 4.23. Compared with the 12C beam, the RBE values for the 9C beam were always higher; an increase in RBE by a factor of up to 1.87 has been observed at the depths distal to the Bragg peak., Conclusion: The potential advantage of radioactive 9C-ion beam in cancer therapy has been revealed at low dose rate in comparison with a therapeutic 12C beam. This observation, however, remains to be investigated at therapeutic dose rates in the future.

The latest heavy ion therapy tends to require information about the spatial distribution of the quality of radiation in a patient's body in order to make the best use of any potential advantage of swift heavy ions for the therapeutic treatment of a tumour. The deflection of incident particles is described well by Molière's multiple-scattering theory of primary particles; however, the deflection of projectile fragments is not yet thoroughly understood. This paper reports on our investigation of the spatial distribution of fragments produced from a therapeutic carbon beam through nuclear reactions in thick water. A DeltaE-E counter telescope system, composed of a plastic scintillator, a gas-flow proportional counter and a BGO scintillator, was rotated around a water target in order to measure the spatial distribution of the radiation quality. The results revealed that the observed deflection of fragment particles exceeded the multiple scattering effect estimated by Molière's theory. However, the difference can be sufficiently accounted for by considering one term involved in the multiple-scattering formula; this term corresponds to a lateral 'kick' at the point of production of the fragment. This kick is successfully explained as a transfer of the intra-nucleus Fermi momentum of a projectile to the fragment; the extent of the kick obeys the expectation derived from the Goldhaber model.

Owing to the potentially therapeutic enhancement of delayed particles in treating malignant diseases by radioactive 9C-ion beam, LET spectra at different penetration depths for a 9C beam with 5% momentum spread, produced in the secondary beam line (SBL) at HIMAC, were measured with a multi-wire parallel-plate proportional counter. To compare these LET spectra with those of a therapeutic 12C beam under similar conditions, the 12C beam was replaced with an 11C beam, yielded in the SBL as well and having almost the same range as that of the 9C beam. The LET spectra of the 9C beam and its counterpart, i.e. the 11C beam, at various depths were compared, especially around the Bragg peak regions. The results show that nearby the Bragg peak lower LET components decreased in the LET spectra of the 9C beam while extra components between the LET peak caused by the primary beam and the lower components due to the fragments could be observed. These additional contributions in the LET spectra could be attributed to parts of the emitted particles from the radioactive 9C ions with suitable conditions regarding the LET counter. Integrating these LET spectra in different manners, depth-dose and dose-averaged LET distributions were obtained for the 9C and 11C beams, forming the basic data sets for further studies. In general, the depth-dose distributions of the 9C and 11C beams are comparative, i.e. almost the same peak-to-plateau ratio. The ratio for the 9C beam, however, has room to increase due to the geometric structure limitation of the present detector. The dose-averaged LETs along the beam penetration are always lower for the 9C beam than for the 11C beam except at the falloff region beyond the Bragg peak. Applying the present depth-dose and dose-averaged LET data sets as well as the essential radiobiological parameters obtained with 12C beams previously for HSG cells, an estimate concerning the HSG cell surviving effects along the penetration of the 9C and 11C beams shows that lower survival fractions for the 9C beam at the distal part of the Bragg peak, corresponding to the stopping region of the incoming 9C ions, can be expected when the same entrance dose is given. It is still hard to appreciate the potential of 9C beams in cancer therapy based on the present LET spectrum measurement, but it provides a substantial basis for upcoming radiobiological experiments.

It is desirable to reduce range ambiguities in treatment planning for making full use of the major advantage of heavy-ion radiotherapy, that is, good dose localization. A range verification system using positron emitting beams has been developed to verify the ranges in patients directly. The performance of the system was evaluated in beam experiments to confirm the designed properties. It was shown that a 10C beam could be used as a probing beam for range verification when measuring beam properties. Parametric measurements indicated the beam size and the momentum acceptance and the target volume did not influence range verification significantly. It was found that the range could be measured within an analysis uncertainty of +/-0.3 mm under the condition of 2.7 x 10(5) particle irradiation, corresponding to a peak dose of 96 mGyE (gray-equivalent dose), in a 150 mm diameter spherical polymethyl methacrylate phantom which simulated a human head.

The (10)C and (11)C beam stop position in a homogeneous phantom was measured using the range verification system in HIMAC. This system was developed to clear uncertainty of beam range within the patient body in heavy ion radiotherapy. In this system, a target is irradiated with RI beams ((11)C or (10)C) and the distribution of the beam end-points are measured by a positron camera. To inspect the precision of the measurement, three experiments were done, simple PMMA phantom irradiation, empirical beam stop position measurements using a range shifter and boundary irradiation using PMMA and lung phantom. Results of the first two experiments were consistent. Consequently, a 0.2 mm standard deviation of statistical error measurement was possible with 250 determinations. For the third experiment, we compared the precision using (10)C and (11)C beams. The boundary of the PMMA and lung phantom was irradiated with both beams to maximize the positron range effect in the beam range measurement. Consequently, no significant difference was observed between the two beams in spite of the different positron range. Thus, we conclude that the (10)C beam was useful for clinical application because of its good statistics owing to the short half-life.

An advantage of heavy-ion therapy is its good dose concentration. A limit for full use of this desirable feature comes from range ambiguities in treatment planning. The treatment planning is based on X-ray CT measurements, and the range ambiguities are mainly due to an error in calibration of the CT number. The heavy-ion ranges are related to electron density of the medium while the CT numbers are defined using the X-ray attenuation coefficient. The range verification method using positron emitter beams has been developed to reduce the range ambiguities. In this verification, probing beams of positron emitters are implanted into the tumor, and pairs of annihilation gamma rays are detected with a positron camera. This paper demonstrates an application to verify treatment planning. Here the treatment planning was made on a head phantom and the ranges estimated from the CT-number were compared with the ranges measured with the positron camera. As a result, disagreements were detected between the planned ranges and the measured ones; there were 1.6 mm at maximum. The disagreements were due to an error of transformation of CT-number to range for the phantom material in the water column depth-dose measurement. The disagreements could be lowered to 0.4 mm by using the calibrated water-equivalent lengths. It was confirmed that the range verification system has a designed measurement accuracy of 1 mm and is useful for verifying irradiation fields on heavy-ion radiotherapy.

Heavy ion therapy has two definite advantages: good dose localization and higher biological effect. Range calculation of the heavy ions is an important factor in treatment planning. X-ray CT numbers are used to estimate the heavy ion range by looking up values in a conversion table which relates empirically photon attenuation in tissues to particle stopping power; this is one source of uncertainty in the treatment planning. Use of positron emitting radioactive beams along with a positron emission tomograph or a positron camera gives range information and may be used as a means of checking in heavy ion treatment planning. However, the metabolism of the implanted positron emitters in a living object is unpredictable because the chemical forms of these emitters are unknown and the metabolism is dependent on the organ species and may be influenced by many factors such as blood flow rate and fluid components present. In this paper, the washout rate of 11C activity implanted by injecting energetic 11C beams into thigh muscle of a rear leg of a rabbit is presented. The washout was found to consist of two components, the shorter one was about 4.2 +/- 1.1 min and the longer one ranged from 91 to 124 min. About one third of the implanted beta+ activity can be used for imaging and the rest was washed out of the target area.

In heavy-ion radiotherapy, an accelerated beam is modified to realize a desired dose distribution in patients. The setup of the beam-modifying devices in the irradiation system is changed according to the patient, and it is important to check the depth dose distributions in the patient. In order to measure dose distributions realized by an irradiation system for heavy-ion radiotherapy, a multi-layer ionization chamber(MLIC) was developed. The MLIC consists of 64 ionization chambers, which are stacked mutually. The interval between each ionization chamber is about 4.1 mm water. There are signal and high voltage plates in the MILC, which are used as electrodes of the ionization chambers and phantom. Depth dose distribution from 5.09 mm to 261.92 mm water can be measured in about 30 seconds using this MLIC. Thus, it is possible to check beam quality in a short amount of time.

The broad-beam three-dimensional irradiation system under development at National Institute of Radiological Sciences (NIRS) requires a small ridge filter to spread the initially monoenergetic heavy-ion beam to a small spread-out Bragg peak (SOBP). A large SOBP covering the target volume is then achieved by a superposition of differently weighted and displaced small SOBPs. Two approaches were studied for the definition of a suitable ridge filter and experimental verifications were performed. Both approaches show a good agreement between the calculated and measured dose and lead to a good homogeneity of the biological dose in the target. However, the ridge filter design that produces a Gaussian-shaped spectrum of the particle ranges was found to be more robust to small errors and uncertainties in the beam application. Furthermore, an optimization procedure for two fields was applied to compensate for the missing dose from the fragmentation tail for the case of a simple-geometry target. The optimized biological dose distributions show that a very good homogeneity is achievable in the target.