E. Urakabe

Washout measurement of radioisotope implanted by radioactive beams in the rabbit.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.

Washout studies of 11C in rabbit thigh muscle implanted by secondary beams of HIMAC

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.

Range verification system using positron emitting beams for heavy-ion radiotherapy

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.

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions

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 patients 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.

The LET spectra at different penetration depths along secondary 9C and 11C beams

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.

Medical application of radioactive nuclear beams at HIMAC

By using the radioactive nuclear beam with relativistic high energy of short-lived positron emitting nuclei, such as C10 and C11, a verification system for the precise radiotherapy has been developed. It is possible to determine the precise particle range and the three-dimensional irradiated area in the human body by a positron camera detector and a positron emission tomography system, respectively. The biological and chemical process of the metabolism is an important parameter for the precise measurement. The biological lifetimes of the C10 and C11 injected into the rabbit’s organs have been observed for the study of metabolism. The microscopic process around the cell is also of interest in the study of biological effectiveness. The observation of the difference between radiological effectiveness of C9 and that of C12 is in progress.By using the radioactive nuclear beam with relativistic high energy of short-lived positron emitting nuclei, such as C10 and C11, a verification system for the precise radiotherapy has been developed. It is possible to determine the precise particle range and the three-dimensional irradiated area in the human body by a positron camera detector and a positron emission tomography system, respectively. The biological and chemical process of the metabolism is an important parameter for the precise measurement. The biological lifetimes of the C10 and C11 injected into the rabbit’s organs have been observed for the study of metabolism. The microscopic process around the cell is also of interest in the study of biological effectiveness. The observation of the difference between radiological effectiveness of C9 and that of C12 is in progress.

Biological effects of radioactive 9C-ion beams on cells

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×l06 and 82.88% respectively with the primary 12Cbeams of 430 MeV/u and 1.8×l09 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 {u12}C-beams. 9C-beams are more efficacious for tumor treatment than 12C-beams.

Physical and engineering aspect of carbon beam therapy

Conformal irradiation system of HIMAC has been up‐graded for a clinical trial using a technique of a layer‐stacking method. The system has been developed for localizing irradiation dose to target volume more effectively than the present irradiation dose. With dynamic control of the beam modifying devices, a pair of wobbler magnets, and multileaf collimator and range shifter, during the irradiation, more conformal radiotherapy can be achieved. The system, which has to be adequately safe for patient irradiations, was constructed and tested from a viewpoint of safety and the quality of the dose localization realized. A secondary beam line has been constructed for use of radioactive beam in heavy‐ion radiotherapy. Spot scanning method has been adapted for the beam delivery system of the radioactive beam. Dose distributions of the spot beam were measured and analyzed taking into account of aberration of the beam optics. Distributions of the stopped positron‐emitter beam can be observed by PET. Pencil beam of t...