The PSIHO Project Photoneutron Source In HOspital Inhospital

The PSIHO Project Photoneutron Source In HOspital In-hospital installation of Dedicated Linac & New Pho. Ne. S photoconverter Gianrossano GIANNINI (giannini@ts. infn. it) Physics Dept. Trieste University and INFN Via Valerio 2, Trieste, 34127, Italy Financially supported by: National Institute for Nuclear Physics • Ministery of Industry, Research and University • Fondazione CRT Torino

Cavity: 20 x 10 cm 3 At present Pho. Ne. S Bianco prototype Lead slabs, thickness 1 mm D 2 O GRAPHITE 50% Epoxy resin slabs, thickness 2 mm GRAPHITE 50% boron carbide slabs LEAD POLYETHILENE MCNP-GN simulation Closed cavity configuration • Two carbon fibre boxes filled with heavy water and a polyethylene slab to close 60 cm Graphite: - 2 horizontal blocks, 15 x 30 x 60 cm 3 - 2 vertical blocks, 15 x 30 cm 3 Thermal neutron field of suitable intensity and energy spectral distribution for biological samples irradiation

Universita’ degli Studi di Torino II Facolta’ di Medicina e Chirurgia ASO San Luigi Gonzaga Orbassano Torino Orbassano –Torino (Italy) BUNKER The hospital was funded in 1818. Since 1970 is situated in the new location. It is leader in the treatment of lung diseases.

Campioni di tessuti polmonari umani, in seguito a rimozione chirurgica presso l’ospedale S. Luigi Orbassano di Torino dopo perfusione con boron-phenyl-alanine arricchita in 10 B (10 BPA) per 2 ore, Campioni ~10 mm di spessore e ~ 1 cm 2 di area preparati su lastrine di CR-39

Convertitore fotoneutronico Pho. Ne. S montato presso il linac Elekta SLIT 25 MV dell’Ospedale Le Molinette di Torino Campioni biologici su CR-39 due strati (37 x 13 x 1 mm 3) esposti a neutroni termici nella cavita’ di Pho. Ne. S

Electa SL 25 25 MV 70000 M. U. @400 M. U. /min 104 s ~ 3 hours PHONES ~1011 n/cm 2

CR-39 ANALYSIS Histological samples on CR-39 detectors and corresponding image of samples after irradiation.

Image processing • Image. J. • Cinema 4 D. • Surfer 8. green>20 ppm blue>40 ppm orange>60 ppm red>80 ppm Colordensitometry

Image-Pro Plus © Microscopic Image Automated Analysis for hole area study and counting

μg/ml (Pavia) or ppm (Trieste/Como) DETERMINATION OF BORON CONCENTRATION AT VARIOUS TIMES AFTER PERFUSION WITH 10 BPA Time, min

Analisi di campioni biologici da tessuto umano trattato con perfusione ex-vivo con BPA per studiare diversi tipi di patologie tumorali (in particolare il mesotelioma) seguendo le indicazioni degli oncologi. Si prevede che nei prossimi decenni (2015) il mesotelioma polmonare (neoplasia della pleura polmonare) diventi uno dei tumori con il più alto tasso di incidenza a causa dell’uso industriale e civile dell’amianto negli ultimi 20 -30 anni. QUESTO ASPETTO E’ DI GRANDE INTERESSE PER LA COMPONENTE OSPEDALIERA. In Regione Piemonte si prevede un numero rilevante di pazienti affetti da tale patologia per la presenza di impianti industriali che utilizzavano o producevano eternit (“Eternit” di Casale Monferrato), e come dimostrato anche da recenti fatti di cronaca (Chivasso (TO), 22/07/08) Le regioni più colpite dal mesotelioma, il cosidetto “mal d’amianto”, sono: Liguria, Friuli Venezia Giulia, Piemonte e Lombardia

Dedicated Linac: advantages & goals • Possibility of full time use of the LINAC overcoming the restriction imposed by radiotherapy departments for the use of clinical accelerators: – Time restriction (following the patients timetable) – Impossibility to modify the machine parameters • For photoneutron production it is not necessary to have an optimized gamma beam (g, n) treashold energy region Neutron photoproduction +1. 5 times higher • Removing filters (flattening and hardening filters) from the linac gantry • Improving the linac duty cycle, (increasing beam current, repetiton rate, pulse duration, etc. ) to obtain • higher gamma fluence rate • higher neutron photoproduction

At present Experimental set-up for biological trials • e-Linac Elekta 25 Me. V max dose rate 400 UM/min • Pho. Ne. S Bianco (weight ~ 400 kg – assembling time ~ 1. 5 ore) • Thermal neutron fluence rate ~ 1 E 7 n cm-2 s-1 • Biologiacl samples: primary lung carcinoma UM total: 70000; Total fluence: ~ 1 E 11 ncm-2; Irradiation Time: ~ 3 hrs BIOLOGICAL SAMPLES INSIDE THE CAVITY The irradiation has been carried out at Radiotherapy Department of San Giovanni Battista Molinette Hospital (Turin, Italy)

FUTURE Pho. Ne. S Optimized Prototype GRAPHITE LEAD HEAVY WATER POLYETHILENE IRRADIATION CAVITY • An optimized geometrical configuration of the various components has been designed. • The high-Z core for neutron production and the low-Z moderating structures are suitably shaped.

Pho. Ne. S Optimized Neutron photoproduction 15 times higher by using Pho. Ne. S optimized prototype and dedicated LINAC Pho. Ne. S Bianco

Pho. Ne. S Bianco vs Pho. Ne. S Optimized Prototype Pho. Ne. S Prototypes Neutron Beam Parameter Pho. Ne. S Bianco Pho. Ne. S Optimized Thermal Neutron Fluence Rate 1. 01 E 7 cm-2 s-1 1. 50 E 8 cm-2 s-1 (78%) (73%) Epithermal Neutron Fluence Rate 2. 18 E 6 cm-2 s-1 4. 08 E 7 cm-2 s-1 (18%) (20%) 5. 88 E 5 cm-2 s-1 1. 43 E 7 cm-2 s-1 (4%) (7%) 3 hrs (1 E 11 ncm-2) 12 min (1 E 11 ncm-2) Fast. Neutron Fluence Rate Biological samples irradiation time

BUNKER INSTALLATION SITE • ASU San Luigi Gonzaga Orbassano (TO) CORRIDOR CONTROL ROOM BUNKER Already built and actually not used for radiotherapy. Proposed by San Luigi Gonzaga hospital for Pho. Ne. S BNCT studies

Conclusion • A dedicated LINAC and an optimized Pho. Ne. S prototype could provide an increase of neutron photoproduction of: • about +1. 5 times by removing filters (flattening and hardening) • about +4 times by increasing LINAC beam power • about +2. 5 times by using Pho. Ne. S optimized prototype • for a total of about 15 times higher in neutron photoproduction 12 min. total thermal neutron fluence rate of 1 E 11 cm-2 FIRST IN-HOSPITAL NEUTRON SOURCE FOR BNCT RESEARCH! (available to the worldwide BNCT scientific community)

Collaboration Institutes Hospitals • • • INFN Torino INFN Trieste Università degli Studi di Torino Politecnico di Torino Università degli Studi di Trieste Università dell’ Insubria di Como • Università degli Studi di Pavia • Universita’ Federico. II di Napoli • Universita’ La Cattolica di Roma • IRCC Candiolo (Torino) • ASO Mauriziano Umberto I° (Torino) • AOU San Luigi – Orbassano (Torino) • AOU San Giovanni Battista (Torino) • ASO Sant’Anna (Como) • Ospedale Maggiore (Trieste) • ST. JOHANNS HOSPITAL Salisburgo Industries ØSORDINA s. p. a. Saonara (PD) ØElekta Company ØTecnologie Avanzate s. r. l. ( Torino)

PSIHO Photoneutron Source In HOspital TRIESTE: Gianrossano Giannini (100%, Resp. Loc. , P. O. ), Erik. Vallazza (20%, P. R. ), Massimo Vascotto (20%, D. S. S. ), A. Zanini (Resp. Naz. , INFN Torino) • Richieste finanziarie locali a Ts (k. E) MI: 9. 0 ME: 4. 0 MC: 6. 0 TR: 2. 0 CA: 8. 0 TOT: 29 • Richieste servizi: Officina Meccanica : S. Reia (2 m/u), D. Iugovaz (1 m/u); Laboratorio Elettronica e Rivelatori : M. Bari (1 m/u)

Torino-Trieste-Como project In-Hospital installation of Dedicated Linac & Pho. Ne. S Optimized Prototype Previous results • Linac accelerators already exist in hospital radiotherapy departments • well-known technology accepted by patients and medical staff • Projects PHONES, NOE 2 supported by INFN from 2005 to 2010 • Encouraging results obtained during: • feasibility study, • first prototype test (Pho. Ne. S Bianco), • first biological trials on human lungs • Great interest by San Luigi Gonzaga hospital (Orbassano, Torino) for BNCT study on lung tumors (adenocarcinoma, mesothelioma) • Availability by Elekta company in order to provide a decommisioned 18 MV Linac and to adapte for BNCT studies • Possibility of installation in radiotheraoy dept. of San Luigi Gonzaga hospital with collaboration and assistance of radiotherapy staff. • Applications in BNCT: • analysis of 10 B uptake in different lung cancer • study of the behaviour and efficacy of different 10 B carriers • Multidisciplinary applications cultural heritage studies, neutron radiography, etc.