Investigation of the biological effectiveness of Boron Neutron Capture Therapy for Head and Neck Cancer

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Boron Neutron Capture Therapy (BNCT) is a biologically targeted form of radiotherapy using the effect of secondary particle radiation released inside tumour cells. The Isotope B-10 has a very high tendency to interact with low energetic neutrons in a fission reaction. The fragments produced in this reaction (a Lithium and an ý-particle) are characterised by their high linear energy transfer (LET) properties and a high relative biological effectiveness in comparison to photon irradiation. If this reaction takes place in a cell, the cell may be severely damaged and die thereafter. The major difference to conventional ý-radiation therapy is the non-radioactive molecule carrying the B-10 isotope which, by externally delivered neutron radiation, makes it possible to generate therapy doses only in predefined tissue volumes. Therapy requires infusion of a specially designed boron compound which selectively enriches in the targeted tumour cells. Then, the most favourable point in time is chosen to irradiate the targeted tissue volume with a low dose of neutrons to release the therapy dose. Usually, BNCT is applied less than three times to a patient, therefore physical and mental stress is greatly reduced compared to other oncological treatment options. Historically, BNCT has been mostly applied to infiltrating brain tumours, but more recently, treatments of malignancies of the head and neck are also being evaluated. Trials carried out in Japan, Taiwan and Finland have shown very promising results. Especially, considerable improvement of the quality of life was reported.The proposal aims at the two parameters of major importance which have to be considered for treatment planning when applying BNCT to head and neck cancer: Investigation of uptake and retention of the boron carrier p-boronophenylalanine during a study with tumour tissue biopsies retrieved from patients undergoing tumour resection; and correlation of these findings with the effect of ionising radiation with high LET compared to ý-rays on the same kind of tissue. Since tumour heterogeneity will be the most decisive parameter to be respected, various analytical methods will have to be used in order to gather sufficient data about boron uptake behaviour in the targeted tissues. This includes studies with biomarkers to characterise the tissues involved accompanied by the determination of amount and distribution of the boron in the respective tissue. Also, the efficacy of an actual treatment of such tumour entities will be investigated by determining the number of cells sustaining DNA damage induced as a consequence of the neutron capture reaction of boron.The results should therefore make it possible to define whether treatment of an investigated tumour entity is possible with respect to the dose released in the targeted cells which ultimately depends on the amount of boron accumulated in the respective tissue and with respect to the damage dealt to the cells on a subcellular level.