Pavia University (Italy) Biology and BNCT: in vivo studies Nano Rosanna Departement of Animal Biology Legnaro, November 17-19, 2009
Efficacy of BNCT in liver metastases t
PROGETTO TAOrMINA Trattamento Avanzato Organi Mediante Irraggiamento Neutronico e Autotrapianto T. Pinelli *, A.Zonta +, S.Altieri *, S.Barni ++, A.Braghieri *, P.Bruschi *, A. Clerici +, P.Chiari ++, C.Ferrari +, F. Fossati *, R.Nano ++, S.Ngnitejen Tata +, P.Pedroni *, U.Prati +++,G.Ricevuti ++, L.Roveda +,C.Zonta + *INFN e Dipartimento di Fisica Nucleare e Teorica, Università di Pavia + Dipartimento di Chirurgia, Divisione di Chirugia Generale, Università di Pavia e Policlinico S. Matteo, Pavia ++ Dipartimento di Biologia Animale Università di Pavia e Centro di studio per l Istochimica CNR Pavia Dipartimento di Biologia Animale, Università di Pavia e Centro di studio per l Istochimica, CNR Pavia +++ Chirurgia Sperimentale e Tecnologie Chirurgiche Innovative IRCCS Policlinico S. Matteo, Pavia
This technique may be applied to different tumor types Japan, U.S.A., Europe: braintumor(gbm) skin melanoma External beams collimated of epithermal neutrons PAVIA Explantable organs: liver lung Irradiation in uniform field of thermal neutrons
TRIGA MARK II Nuclear Reactor University of Pavia
EXPERIMENTAL STUDY IN VIVO
MATERIALS AND METHODS CELL LINE DHD/K12/TRb / CELL LINE HAS BEEN ESTABLISHED FROM A RAT COLON-CARCINOMA CHIMICALLY INDUCED (1,2 dimethylhydrazine ) IN A BD-IX STAIN RATS. THIS LINE WAS SELECTED AND CLONED FOR ITS CAPACITY TO INDUCE PROGRESSIVE AND METASTATIC TUMOURS IN THE SYNGENEIC HOST.
DHD/K12/TRb Morphology of the cultured cells stained with MGG M.G.G.
Rat liver sample: normal (A) and tumoral (B) A Samples stained with E&E B
ELECTRON MICROSCOPE
Tumoral cells observed by electronmicroscopy. The cells formed as a nest.
FREE TUMORAL CELLS BEFORE IRRADIATION
APOPTOTIC TUMORAL CELLS AFTER IRRADIATION
Stromal reactivity After transplantation of the liver
After transplantation of the liver Collagen bundles
Metastatic nodule with apoptotic cells After transplantation t ti of the liver
Activated Kupffer Cells
Activated Kupffer Cells
Example of rat liver metastases The liver metastases are spread in the whole oe organ After BPA infusion It is important to quantify the 10 B concentration In the tumor C T In the normal liver C S T = C T C S
Selective absorption of 10 B: neutron autoradiography Histological sample Neutron autoradiography Rat liver
Selective absorption of 10 B: neutron autoradiography Histological sample Neutron autoradiography Rat liver
METASTASES IMAGING, human liver Healthy liver Liver with metastases 3 mm 9 mm 12 mm Neutron radiography
Sequence: sample layers every 40 μm Here we can clearly see the tumor evolution when going deep inside the tissue 1 2 3 4 5 6
A very little metastasis All metastases absorb the boron: also those having sizes of a few tenth of mm 16 mm 0.25 mm
The first patient (2001) Biopsy during the operation
The moment of the exit of the liver from the Triga reactor of Pavia.
2002 January 25, the patient visits the nuclear reactor after 37 day of the treatment
The first patient (2003) ) Biopsy after BNCT treatment
The second patient (2003) Biopsy during the operation
The second patient (2003) Biopsy during the operation
Post-mortem examination after BNCT treatment (2003)
Post-mortem examination after BNCT treatment (2003)
Post-mortem examination after BNCT treatment (2003)
cancer stem cells
Histiocytic activation following neutron irradiation of boron-enriched rat liver metastases. Nano R, Barni S, Gerzeli G, Pinelli T, Altieri S, Fossati F, Prati U, Roveda L, Zonta A. Ann N Y Acad Sci. 1997 Dec 15;832:274-8. Efficacy of boron neutron capture therapy on liver metastases of colon adenocarcinoma: optical and ultrastructural study in the rat. Nano R, Barni S, Chiari P, Pinelli T, Fossati F, Altieri S, Zonta C, Prati U, Roveda L, Zonta A. Oncol Rep. 2004 Jan;11(1):149-53. Neutron autoradiography imaging of selective boron uptake in human metastatic tumours. Altieri S, Bortolussi S, Bruschi P, Chiari P, Fossati F, Stella S, Prati U, Roveda L, Zonta A, Zonta C, Ferrari C, Clerici A, Nano R, Pinelli T. Appl Radiat Isot. 2008 Dec;66(12):1850-5. Epub 2008 May 29 Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases. Bakeine GJ, Di Salvo M, Bortolussi S, Stella S, Bruschi P, Bertolotti A, Nano R, Clerici A, Ferrari C, Zonta C, Marchetti A, Altieri S. Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S332-5. Epub 2009 Mar 27.