1. Page  1 A new method to measure 10 B uptake in lung adenocarcinoma in hospital BNCT D. Bolognini, E.M. Donegani, A. Mattera, M. Prest, S. Hasan E. Capelli, P. Chiari A. Zanini G. Giannini, E. Vallazza F. Basilico, P. Mauri F. Borasio P. Cappelletti, M. Frigerio, S. Gelosa, A. F. Monti

2. Page  2  BNCT  The INFN PhoNeS project  An innovative approach to Boron Imaging  Neutron Autoradiography  Measurements and results  Conclusion Outline

3. Page  3 Boron Neutron Capture Therapy BNCT could become useful for highly-fatal tumours: Extended (e.g. liver, lung) Radioresistant (melanoma) Localized near vital organs (glioblastoma) 10 B (n,α,γ) 7 Li binary technique high LET particles

4. Page  4 High intensity thermal-epithermal neutron beam (5·10 8 n/cm 2 s 1 ) < 10 keV energy range Gamma contamination < 2 ·10 -13 Gy cm 2 / n Low toxicity High specificity Non-persistence in the bloodstream BSH BPA Difficulties for BNCT applications

5. Page  5 Neutron Autoradiography  Nuclear reactor  Solid state track detector (CR 39)  Sometimes cryogenic temperature during the irradiation  Optic microscope for identification and count  Nuclear reactor  Solid state track detector (CR 39)  Sometimes cryogenic temperature during the irradiation  Optic microscope for identification and count  Hospital-based neutron source  Real time detector  Hospital-based neutron source  Real time detector

6. Page  6 PhoNeS ( PhotoNeutronSource ) Neutron flux in the treatment cavity: Φ = (1.3 ± 0.1) x 10 7 n cm -2 s -1 γ-contamination: reduced of 97%

7. Page  7 Real-time Neutron Autoradiography 0.5 cm CERROBEND photonconversion 6 cm PMMA thermalization IRON BOX Samples Detector Neutron flux: Φ = (1.5 ± 0.1) x 10 5 n cm -2 s -1

8. Page  8 The imaging detector Silicon Dimensions(9.5 x 9.5) cm 2 Hamamatsu Microstrip Silicon Detector768 strips Readout pitch242 μm Read-out by3 self-triggering TAA1 ASICs Counts vs position

9. Page  9 The Data Acquisition System INTER-BUNCH acquisition UNDEPLETED silicon detector to detect α-particles from boronated samples down to 25 ng of 10 B 18 MeV electrons Bunches of 5 μs Frequency 100 - 300 Hz

10. Page  10 SPECIMEN SUPPORT -plastic support (liquid solution) evaporation -glass slide (blood samples) coagulation process to prevent crystallization and self-absorption of the α-particles by the sample itself KNOWN VOLUME Drops of 5 μl The samples SOLUTION HOMOGENEITY

11. Page  11 Calibrating with BSH 500 MU/min –18 MV photons Varian CLINAC 2100 C/D, Sant’Anna Hospital (Como) Integrated Spot Content (AU) vs Concentration (ppm)

12. Page  12 The first ever kinetic curves Special thanks to Dr.Sauerwein URINEBLOOD rescaled at the max value obtained by Si-autoradiography Blood and urine of a patient administered BSH, taken at different times with respect to the administration.

13. Page  13 Ex-vivo lung perfusion Human lung affected by adenocarcinoma: therapetic resection perfusion of blood and BPA Blood samples taken at different times: to estimate 10 B uptake in collaboration with “S.Luigi” Hospital in Orbassano (TO), Italy

14. Page  14 Kinetic curves Blood samples doped with BPA Comparison between real-time autoradiography to MS analysis The absorption takes place only in the first 90mins

15. Page  15 CR 39 Healthy tissue Unhealthy tissue Special thanks to Dr. Giannini 10 B concentration in tumour and healthy tissues of resected lobe High-resolution images to reproduce the features of the tissues C T / C H ~ 1.5 - 2

16. Page  16 Conclusions  Neutron Autoradiography in a hospital environment successfully performed - Linac  Development of an hospital-base neutron source to perform Boron Imaging with a 1D spatial resolution  Real-time detector to perform pharmacokinetic studies results during the irradiation  Blood samples from a perfused lung affected by adenocarcinoma kinetic curves - 10 BPA down to concentrations of 5ppm  Evaluation of 10 B concentration in tumour and healthy tissues Si-autoradiography – CR 39  Looking forward to make BNCT possible in every radiotherapic unit

17. Page  17 A new method to measure 10 B uptake in lung adenocarcinoma in hospital BNCT D. Bolognini, E.M. Donegani, A. Mattera, M. Prest, S. Hasan E. Capelli, P. Chiari A. Zanini G. Giannini, E. Vallazza F. Basilico, P. Mauri F. Borasio P. Cappelletti, M. Frigerio, S. Gelosa, A. F. Monti Thank you!