1. The segment of the TOP-IMPLART accelerator up to 150 MeV has been funded by Regione Lazio and is under realization at ENEA- Frascati Center choose as a test site. The accelerator is based on the 7 MeV injector consisting in a 3 MeV RFQ followed by a DTL up to 7 MeV (PL-7ACCSYSHITACHI model) followed by a vertical and an horizontal beam transport line matching the beam to the following accelerating modules. TOP-IMPLART LINEAR ACCELERATOR FOR PROTON THERAPY: LAYOUT AND FIRST RADIOBIOLOGICAL RESULTS AT LOW ENERGY Maria Antonella Tabocchini 1, Alessandro Ampollini 2, Giulia Bazzano 2, Francesca Marracino 2, Concetta Ronsivalle 2, Monia Vadrucci 2, Maria Balduzzi 3, Clarice Patrono 3, Claudia Snels 3, Antonella Testa 3, Pasqualino Anello 1, Cinzia De Angelis 1, Giuseppe Esposito 1, Marco D’Andrea 4, Lidia Strigari 4 7 MeV 150 MeV 35 MeV 230MeV Head-Neck Tumors Head-Neck Tumors In-vitro and in-vivo Radiobiology In-vitro and in-vivo Radiobiology In vitro Radiobiology In vitro Radiobiology 18 MeV Deep Tumor The section of the accelerator up to 11.6 MeV module, is already installed and has been tested. Additional modules will be added to the injector leading proton energy to 30, 70 and 150 MeV in a step by step project. ….. The 7 MeV injector proton beam was used for radiobiology experiments devoted to a biological characterization of the beams in terms of the cell killing. A dedicated radiobiology vertical beam line has been implemented. To this purpose, a 90° vertical bending magnet is placed in the middle of the low energy beam transport line. In this way it is possible to select the requested energy of protons impinging on the cells. The first radiobiological experiments were carried out to characterize the proton beam. To this purpose, cell killing experiments were conducted at the TOP-IMPLART vertical transport line on V79 and CHO cells. Irradiations have been performed with protons extracted in air and impinging on the cells with energy of 5 MeV (incident LET=7.7 keV/μm in MS20); the clonogenic survival was evaluated in the dose range 0.5-8 Gy. 90° magnet Acknowledgements: Thanks are due to FILAS-Regione Lazio for funding the TOP-IMPLART Project, coordinated by L. Picardi, C.Marino (ENEA) and E. Cisbani (ISS), and to R.Cherubini (LNL-INFN) for his prime scientific support. Sample holderBeam line 1 Istituto Superiore di Sanita (ISS) and INFN-Gr.coll.Sanita (Italy), 2 ENEA-Frascati, Rome (Italy), 3 ENEA- Casaccia, Rome (Italy), 4 Regina Elena National Cancer Institute, IFO, Rome (Italy) INFN-LNL radiobiology irradiation setup (in air): single sample holder and set of sample holders placed on the revolving system remotely controlled during measurements. The same sample holders especially designed for proton irradiation at the LNL (Belli et al, Nucl Instr Meth 1987) have been used at the TOP-IMPLART during irradiation of Chinese hamster cells with protons of 5 MeV, corresponding to an incident LET (in MS20 tissue) of 7.7 keV/µm. Gaf-Chromic EBT3 film have shown a uniformity of 90% on the irradiated area. Calibration curves Dose vs. netOD of the EBT3 films irradiaed at the LNL with 5MeV protons at the dose rate of 2.1 Gy/min LAYOUT FIRST RADIOBIOLOGICAL RESULTS DOSIMETRY  : 0.208 ± 0.016 β: 0.020 ± 0.003 FUTURE DEVELOPMENTS TOP (Oncological Therapy with Protons) - IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTherapy) project curried out by ENEA, ISS and IFO as the end-user, is based on a compact pulsed 230 MeV proton LINAC designed for fully active scanning (3+1)D in intensity (instantaneous released dose), energy (depth) and transversal position (x-y). Peculiar characteristics of the system are: modularity, pulsed operation naturally suited to IMPT, fast energy variation, high quality beam, high dose rate capability, reduced beam losses and reduced neutron production along the accelerating sections. The TOP-IMPLART proton beams will also be used for in vivo” and “in vitro” radiobiological studies. DOSE DELIVERY MONITOR OF THE TOP-IMPLART PROTON THERAPY BEAM A dose delivery monitor was specifically designed for the TOP IMPLART beam characteristics. It will measure the beam intensity profile, position and direction to monitor the fully active 3+1D (x, y, z and intensity) pulsed beam. The monitor system consists of segmented ionization chambers and it is driven by dedicated electronics. Assembled chamber prototype First electron beam tests of the chamber prototype of the dose delivery monitor show good noise characteristics and excellent beam profile measurements. Further and more accurate characterization tests are in progress, while a new, consolidated version of the chamber and the electronics is under development. SCATTERING CHAMBER AND MULTISAMPLE HOLDER Energy measurement of a proton beam after a scattering process The scattering process happens inside a scattering chamber with a vacuum of P~ 10 −3 Pa. Target and detectors can be moved inside the chamber. The energy of the scattered proton is measured by a Lithium drifted Silicon detector with 5 mm of thickness. The angle is determined by a mechanic positioning system of the detector that uses a quadrature encoder with a resolution better than 0,004 degrees. The dose-response curves for clonogenic survival were found to be characterized by an initial shoulder (more pronunced in V79 than in CHO cells) followed by a straight portion, that can be well fitted by a linear-quadratic function of the dose. The results on V79 cells, widely used in hadrontherapy experiments, were found in good agreement with the previous data obtained at LNL. Also the data obtained using CHO cells were consistent with literature results (Tang et al., British Journal of Cancer 1997). Experiments are planned with a differernt proton energy to extend the radiobiological characterization of the TOP-IMPLART proton beam.  : 0.186 ± 0.019 β: 0.090 ± 0.003 Dosimetry was carried out using GafChromic EBT3 films, calibrated at the INFN-LNL Laboratories with a proton beam having the same energy, at the entrance of the EBT3 film, as the protons produced by the TOP-IMPLART accelerator for these radiobiological experiments. (Vadrucci et al., accepted for pubblication in Medical Physics) V79 (4 exps) CHO (3 exps) Dose to MS20 (Gy) netOD Belli et al., International Journal of Radiation Biology 1999 Fig.1 Survival curves for V79 cells irradiated with X-rays and protons with different LET. Each data point represent the mean of at least seven independent experiments and the error bars denote one standard error of the mean.  : 0.208 ± 0.017 β: 0.020 ± 0.003 Table 2 Parameters obtained from the best fit od the s rvival curves RBE-LET relationship for cell inactibation and mutation induced by low energy protons in V79 cells: further results at the LNL facility mylar foil protons cell monolayer