Boron Neutron Capture Therapy

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It is clear that by shielding the central part of the neutron irradiation eld, it is possible to improve the relative depth distribution of neutrons (compare the doses at points A and B with and without the center shield).Along with the development of new boron compounds, import-ant issues for BNCT include basic research to expand the application of existing compounds to common cancers and develop targeting techniques for using them effectively. Boron compounds exhibit a complex microscopic distribution, and the boron accumulation and dose vary with the types of cells that constitute normal tissue. Present research into the biological effects of radiation has not revealed how damage to individual types of cells contributes to overall tissue damage. Conse-quently, it is standard practice in BNCT to calculate a virtual dose based on the concentration of boron in the blood and the neutron fluence to the tissue, and then the X-ray equivalent dose is calculated by multiplying the virtual dose by a conver-sion coefficient. This coefficient indicates the effective relative biological effectiveness (RBE) of BPA or BSH, and it is known as the compound biological effectiveness (CBE) factor. Since the CBE factor changes depending on the kind of boron compound used and the type of tissue evaluated, it is deter-mined by means of animal experiments. Japanese researchers have determined CBE factors of BPA for the skin and hepato-cytes and of BSH for hepatocytes. This data has enabled BNCT to be used to treat malignant melanoma and liver cancer.In order to facilitate the selective accumulation of boron compounds in tumors, KUR researchers devised the idea of applying the IVR procedure. It succeeded in selectively confin-ing BSH to an experimental liver cancer using the IVR proce-dure, and a boron concentration ratio of about 70 was attained. In BNCT treatment of head and neck cancers, researchers are attempting to inject boron compounds into tumor arteries to facilitate super-selective drug delivery. Unlike X-rays and heavy charged particle radiation, neutrons disperse like mist in the body upon irradiation. Consequently, their depth distribution can be improved by using techniques that seem counterintuitive from experience with X-rays and other kinds of radiation.By non-invasive injection of air into the dead space left after tumor resection, the depth distribution of neutrons can be improved, allowing BNCT to be used to treat deep tumors as well. When the size of the dead space is large, this technique is extremely effective (see gure below). The dose at point A has been increased from 30 Gy-eq to 40 Gy-eq.Normal liverTumor10B accumulation ratio = 68With air injectionWithout air injectionAAThe following figure illustrates the standard BNCT procedure for use in treating a malignant brain tumor, including prior medical examination, image inspection using CT and MRI, and confirmation of diagnosis by using FBPA PET.Development of Compound Biological Effectiveness (CBE) factor and basic technologies in JapanOur BNCT procedure (using a malignant brain tumor as an example)Basic, clinical research and technological developDeadspaceDeadspace10B(n,α) 7Li BPA BSH3.82.51.350.372.50.84.90.32.3？4.30.9TumorRadiation typeBrainSkinMucousmembraneLungHepatocytePostoperative MRIBPA (500 mg/kg)2 hours before start of neutron irradiation (200 mg/kg/h)During neutron irradiation (100 mg/kg/h)MRIFBPA PETPrediction of T/N(B)Injection of air intopostoperative dead space Administration of BSH (±)12 hours before BNCTSimulation of dose distributionbutionBNCTKyoto University Research Reactor (Institute)MRIFBPA PETEvaluation of initial effect Surgery(histopathology diagnosis)Neutron irradiationAdditional X-ray therapy2 Gy/day, 24 GyTMZ75 mg/m2/dayTMZ200 mg/m2/day 5/28 day●15 min. of neutron irradiation ●Measurement of induced radioactivity in a gold wire ●Calculation of uence ●Measurement of boron concentration in the blood ●Determination of irradiation time3

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