Feasibility Studies on the In-vivo Experiments at the Mc-50 Cyclotron Using a Prototype Lept System*

A prototype LEPT (Low Energy Proton Therapy) system was developed and installed at the MC-50 cyclotron in 2007. Some of the users of the PEFP (Proton Engineering Frontier Project) have been requiring an invivo irradiation system for the utilization in the fields of medical and biological sciences [1]. We are studying on the possibility of in-vivo experiments by using the prototype LEPT system. The developed LEPT system consists of collimators, range shifter, rotating modulator for SOBP (Spread Out Bragg Peak), etc. We added a ridge-filter type modulator, a depth-dose measurement system, a mouse holder, boluses, and a collimator for the in-vivo experiments. The energy and current from the cyclotron was 45 MeV and a few nA. For the in-vivo experiments, accurate control of dose rate and penetration depth range is essential. The other important issue is how we can control the irradiation area and volume with high uniformity and accuracy. We investigated the dose distribution inside a samples using PMMA phantom, bolus, and depth-dose measurement system. The absorbed doses were measured by using ionization chamber and GAF films. The dose rate was 0.2~1 Gy/sec and the penetration depth was 10~15 mm. The first in-vivo experiments for the LLC (Lewis Lung Cancer) inoculated C57 mice by using this system was performed successfully. INTRODUCTION Proton therapy is widely acknowledged as one of the most effective methods in the selective destruction of cancer cells. [2] In Korea, a 230MeV cyclotron was imported and installed at the NCC (National Cancer Center) for the proton therapy in 2006 and treatment of patients began in March, 2007. [3] More than 250 patients were treated by using this machine, and the scientists who are interested in proton therapy have been increased continuously. But the experiments for proton therapy were limited to the in-vitro level because there’s no dedicated facilities for in-vivo experiments. For this reason, development of the in-vivo experiment was strongly requested by the PEFP’s users during last few years. To satisfy users’ requirements, we developed invivo experiment system and installed it at the MC-50 cyclotron using the prototype LEPT and some components necessary for in-vivo experiments. DEVELOPMENT OF IN-VIVO EXPERIMENT SYSTEM LEPT Beamline at the MC-50 Cyclotron Figure 1: 45MeV PEFP beam line installed at the MC-50 cyclotron of KIRAMS. ___________________________________________ * Work was performed as a part of Proton Engineering Frontier Project and supported by the MEST (Ministry of Education, Science and Technology) of the Korean government # [email protected] LEPT prototype Mouse holder l Depth-dose measurement system Ionization chamber I i i Monitoring Camera i i Collimator lli Ridge Filter type modulator (For SOBP) i il l The prototype LEPT system was installed at the MC-50 cyclotron of KIRAMS to support basic and pilot studies on proton therapy in the fields of medical and biological sciences in 2007. It was composed of rotating modulator, range shifter, collimator, etc. For in-vivo experiments, we had to add some components necessary to control and measure the depth-dose profiles inside a tumor mass. The whole system is shown in Fig. 1. As shown in figure, TU6PFP010 Proceedings of PAC09, Vancouver, BC, Canada 1312 Applications of Accelerators U01 Medical Applications ridge filter type modulator, depth-dose measurement system, mouse holder, and monitoring camera were added. Ridge-Filter Type Modulator To deliver uniform dose to the sample volume, beam scanner and modulator combined. When use this kind of method, ridge-filter type modulator is more convenient because of there’s no time sharing effect. Uniform dose distribution in depth as well as in lateral and vertical direction can be made unrelated the timing shape of beam scanning instruments. And another unique aspect of this ridge filter type modulator is it can make uniform depthdose distribution from the surface to the planned depth. The design of the ridge and processed shape are shown in Fig. 2 with the photograph of the whole system. It was made of pure Al and was designed by using MCNPX code calculation. The maximum thickness of the ridge is 6 mm in consideration of 45-MeV proton beam incidence for the maximum value. Figure 2: Photograph of ridge-filter type modulator and design drawings. The depth-dose distribution and lateral dose distribution were shown in Fig. 3, which was realized by combining with wobbler scanning method and energy degrader. The dose distribution had more than 85% uniformity in both directions. Figure 3: Dose distribution with wobbler scanning method (a) lateral direction and (b) depth. Depth-Dose Measurement System There are many kinds of methods to measure the depthdose profile inside a volume of target. The most general method in hospital is to use water phantom and ionization chamber. But it is not easy to handle and to control because of the big size and water. Another more convenient method is to use film stack made of many sheets of thin radio-chromic films, such as, MD-55, HD810, and EBT. But it is just for single usage. To make up for these weak points in the current depth-dose measurement system explained previously, we developed a depth-dose measurement system by using plastic phantom and ionisation chamber as shown in Fig. 4. Figure 4: Depth-dose measurement system composed of two-kinds of PMMA phantom and ionisation chamber. The PMMA phantom consists wedge-shaped and platetype ones. The PMMA thickness can be controlled in the range from 2.2 ~ 14.8 mm for wedge-shaped phantom. For plate-type phantom, it was composed of six sheets of different thickness, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6 mm. The range of total thickness made by combination of multiple sheets is 0.05 ~ 3.15 mm in step of 0.05 mm. The ionisation chamber was PTW Markus 23343 with 0.055cm measuring volume and 6-mm aperture. This system was controlled by computer using LabView program. The measured depth-dose distributions are shown in Fig. 5 for 41.7 MeV proton beam. Figure 5: Results of depth-dose Profile Measurement (a) w/o SOBP and (b) w/ SOBP. Bolus and Mouse Holder For in-vivo experiments for small animal, mice, mouse holder was manufactured. The mouse holder has 25 mm aperture for proton beam incidence. Inside the aperture bolus and collimator to restrict the proton beam to the tumor volume were inserted. To verify the bolus design, we investigate the proton beam size and range by using PMMA phantom which has sloped aperture as shown in Fig. 6. The beam profile and dose rate were measured by using film stack composed of eighteen 0.1-mm thick HD810 GAF films and seventeen 0.65-mm thick PMMA sheets. The schematics and results of these measurements are shown in Fig. 7. The results are agreed well with the calculation results as expected. 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