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In proton beam therapy precise knowledge of the proton beam range is essential to guarantee the treatment’s efficacy and to avoid unnecessary toxicities. Unlike photon beams, protons stop inside the patient’s body, therefore a direct detection of the distal fall-off is impossible. One technique to determine the beam range is to detect the prompt gamma (PG) rays emitted from the nuclei de-exciting following proton bombardment [1] . PG emission is almost instantaneous and has a high-production rate. The aim of this project is to develop a new method, based on an optimized PG detector system, which can achieve 3D range determination with an uncertainty of no more than 2 mm. The presented method is based on the detection of discrete gamma-rays. As a first step, the position reconstruction capability of the PG detector system was examined by means of Geant4 simulations. The prototype system is comprised of 12 LaBr 3 (Ce) detectors. The information recorded by each individual detector is fed into a reconstruction algorithm to determine the gamma-ray emission point in 3 dimensions. The development of the algorithm, proof-of-principle and simulation validation, have all been conducted using a sealed 60 Co source. Our simulations demonstrate that an ideal detector system with the current reconstruction algorithm is capable of determining the source position with sub-millimetre accuracy. Having obtained proof-of-principle for the reconstruction algorithm the next stage is to investigate how implementing a realistic detector system affects the reconstruction performance. In addition, the ability of the detector system to discriminate between multiple sources in different positions is under evaluation.

INTRODUCTION: The interaction between an epithermal neutron beam, now deliverable with LINAC technology, and tumour cell accumulated Boron from borono-phenylalanine (BPA), releases an intracellular alpha particle and Li ion causing irrecoverable double strand DNA breaks, insensitive to hypoxia and cell cycle state. Augmented uptake of BPA in GBM cells due to LAT1 upregulation allows targeting of tumour cells, but optimisation of BPA delivery, and neutron exposure time, need clarification before a Phase I trial. METHOD: A pharmacokinetic (Pk)study of newly formulated BPA delivered by iv or close arterial infusion with preinfusion barrier opening, has been carried out in 10 new GBM patients. Plasma, ECF microdialysis, LAT1 activity, Tumour and brain around tumour (BAT) boron10 concentrations of have been used to model the optimum period for neutron beam therapy. RESULTS: 75% of GBM cells are LAT 1 positive, many more than the proliferative index PCNA. Pk studies indicate a three compartment model of BPA cell uptake rate limited by LAT1 exchange kinetics plateauing at four hours. LAT 1 density determines cell Boron dose. LAT1 uptake activity varies between core tumour cells and BAT tumour cells. LAT1 expression maybe particularly elevated in patients with unmethylated MGMT promoter. CONCLUSION: Patients with >50% LAT1 expression are likely to benefit from BNCT with non-LAT1 cells best treated with reduced fraction RT. The BPA uptake pattern favours BAT region tumour cells: those left after surgery regardless of -oxic or cell cycle status. BNCT offers a way of RT dose escalation to discontiguous GBM cells avoiding normal brain, exploits the biology of LAT1 and may offer benefit to patients unresponsive to Temozolomide.