In Vivo Efficacy Test of the BNCT Treatment Mediated by an Innovative Dual GadoLinium/Boron Agent

An innovative dual BNCT agent (Gd/B/L-LDL) was developed and its efficacy as 10B carrier was tested by some in vivo irradiations at the TRIGA reactor in Pavia. A localized subcutaneous melanoma is induced in the neck of C57BL/6 mice by the injection of 106 B16 cells. 6 hours before the irradiation the mice receive a bolus of Gd/B/L-LDL at a dose of 0,1 mmolkg-1 in term of Gd content. Two control groups are foreseen: one of irradiated mice with no Gd/B/L-LDL infusion, one of not irradiated mice. 3 hours before the irradiation, all the animals enriched with the molecule are subjected to MRI analysis for the 10B concentration measurement. Because of the isotropic thermal neutron field available at the Pavia reactor, it is necessary to design a suitable shield to protect the healthy districts of the animals. The irradiation plan design was realized using the simulation program Monte Carlo N-Particles (MCNP). A geometrical phantom of the mouse was created to estimate the neutron fluxes and the various dose components of the total physical dose deposited in the radiosensitive organs (lung, liver and intestine). Because the Gd/B/L-LDL uptake in the liver is as high as in the tumour, the shield must be extremely effective in sparing the abdomen region. The validation of the code and the efficacy test of the shield have been made by neutron activation of Cu wires. The final irradiation plan foresees an anatomical cylindrical shield made of 99% 10B enriched boric acid with a ring hole around the neck. The shield thickness is equivalent to 0.14 g/cm2 of boric acid. Up to five mice are irradiated simultaneously, using a 45° rotated Teflon support to improve the tumour exposure. The MRI analysis at 6 hours after the Gd/B/L-LDL infusion shows a 10B concentrations ratio between the tumour and the muscle of 3.4, while the same ratio between the tumour and the liver is around 1. For both the irradiated groups, the irradiation time was of 7 minutes at 250 kW. In the aforementioned conditions, the physical doses foreseen by the MCNP simulation are 11.2 Gy in the tumour and 3.7 Gy in the liver. The follow up of the animals shows the efficacy of the new NCT agent, Gd/B/L-LDL. The presented BNCT treatment is under further development. Some tests on 95% 6Li enriched Lithium carbonate are on-going to realize new shields that avoid the secondary γ emission of the 10B capture reaction that represents the main constraint of the irradiation time. At the same time, the synthesis of the molecule with the 157Gd isotope has been realized to take advantage of a combined Gd-NCT and B-NCT therapy.