ABSTRACT
The assessment of boron microdistribution is essential to evaluate the suitability of boron neutron capture therapy (BNCT) in different biological models. In our laboratory, we have reported a methodology to produce cell imprints on polycarbonate through UV-C sensitization. The aim of this work is to extend the technique to tissue samples in order to enhance spatial resolution. As tissue structure largely differs from cultured cells, several aspects must be considered. We studied the influence of the parameters involved in the imprint and nuclear track formation, such as neutron fluence, different NTDs, etching and UV-C exposure times, tissue absorbance, thickness, and staining, among others. Samples from different biological models of interest for BNCT were used, exhibiting homogeneous and heterogeneous histology and boron microdistribution. The optimal conditions will depend on the animal model under study and the resolution requirements. Both the imprint sharpness and the fading effect depend on tissue thickness. While 6 h of UV-C was necessary to yield an imprint in CR-39, only 5 min was enough to observe clear imprints on Lexan. The information related to microdistribution of boron obtained with neutron autoradiography is of great relevance when assessing new boron compounds and administration protocols and also contributes to the study of the radiobiology of BNCT.
ABSTRACT
PURPOSE: We previously reported the therapeutic efficacy of Sequential Boron Neutron Capture Therapy (Seq-BNCT), i.e., BPA (boronophenylalanine) - BNCT followed by GB-10 (decahydrodecaborate) - BNCT 1 or 2 days later, in the hamster cheek pouch oral cancer model. We have utilized the neutron autoradiography methodology to study boron microdistribution in tissue. The aim was to use this method to evaluate if the distribution of GB-10 is altered by prior application of BPA-BNCT in Sequential BNCT protocols. MATERIALS AND METHODS: Extensive qualitative and quantitative autoradiography analyses were performed in the following groups: G1 (animals without boron); G2 (animals injected with BPA); G3 (animals injected with GB-10); G4 (same as G3, 24 h after BPA-BNCT); and G5 (same protocol as G4, 48 h interval). RESULTS: A detailed study of boron localization in the different tissue structures of tumor, premalignant and normal tissue in the hamster cheek pouch was performed. GB-10 accumulated preferentially in non-neoplastic connective tissue, whereas for BPA neoplastic cells showed the highest boron concentration. Boron distribution was less heterogeneous for GB-10 than for BPA. In premalignant and normal tissue, GB-10 and BPA accumulated mostly in connective tissue and epithelium, respectively. CONCLUSIONS: BPA-BNCT could alter boron microlocalization of GB-10 administered subsequently. Boron targeting homogeneity is essential for therapeutic success.