Alteration of the blood-brain barrier after irradiation: implication in boron neutron capture therapy

The radiobiological and clinical data concerning the alteration of the blood-brain barrier (BBB) after cerebral irradiation are reviewed. Several boron neutron capture therapy (BNCT) programs are at present under study in Europe and in the USA. In these programs, irradiation is considered to be delivered in several fractions, and one could also imagine, in principle, delivering BNCT after a full course of external radiotherapy of the brain. These options raise the question of the alteration of the normal BBB by previous irradiation. Before starting clinical applications, it then becomes necessary to assess the integrity of the BBB after different dose ranges and fractionation schemes, and after different time intervals following irradiation. Extrapolation of the available radiobiological and clinical data suggests that for rather small hydrophilic compounds, such as BSH or L-BPA, an early increase in transport through the BBB may be foreseen after single photon dose larger than 10 Gy or after a full standard radiotherapy regimen. However, there is no evidence that the first fractions of a BNCT application (typically 2 to 4 Gy equivalent per fraction) would increase the permeability of the BBB sufficiently to permit transport of large boronated compounds such as porphyrins or antibodies, or even of smaller hydrophilic compounds such as BSH and L-BPA. It can be concluded that the dose selectivity of BNCT is unlikely to be compromised by early alteration of the BBB due to the first fractions of a typical BNCT fractionated regimen.