Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours.

Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and α-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

Calculations of dose distributions in the lungs of a rat model irradiated in the thermal column of the TRIGA reactor in Pavia.

To test the possibility to apply boron neutron capture therapy (BNCT) to lung tumors, some rats are planned to be irradiated in the thermal column of the TRIGA reactor of the University of Pavia. Before the irradiation, lung metastases will be induced in BDIX rats, which will be subsequently infused with boronophenylalanine (BPA). During the irradiation, the rats will be positioned in a box designed to shield the whole animal except the thorax area. In order to optimize the irradiation set-up and to design a suitable shielding box, a set of calculations were performed with the MCNP Monte Carlo transport code. A rat model was constructed using the MCNP geometry capabilities and was positioned in a box with walls filled with lithium carbonate. A window was opened in front of the lung region. Different shapes of the holder and of the window were tested and analyzed in terms of the dose distribution obtained in the lungs and of the dose absorbed by the radiosensitive organs in the rat. The best configuration of the holder ensures an almost uniform thermal neutron flux inside the lungs (Phi(max)/Phi(min)=1.5), an irradiation time about 10 min long, to deliver at least 40 Gy(w) to the tumor, a mean lung dose of 5.9+/-0.4 Gy(w), and doses absorbed by all the other healthy tissues below the tolerance limits.