Neutron autoradiography to study boron compound microdistribution in an oral cancer model

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.

Keywords::

• Neutron autoradiography
• boron microdistribution
• Sequential BNCT
• GB-10
• BPA
• oral cancer

Acknowledgements

The authors gratefully acknowledge the expert advice of Dr Rómulo L. Cabrini on tissue sectioning and of Dr Maria E. Itoiz on histological analysis. The authors are also grateful for the support of Dr Claudio Devida and his team with ICP-MS measurements.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.