Pharmacokinetics and Biodistribution in Patients with Malignant Glioma after Administration of N-Acetylcysteine (N-AC) Prior to Borocaptate Sodium (BSH)
The principle of Boron Neutron Capture Therapy (BNCT) is based on the nuclear reaction that occurs when 10B, a stable isotope, captures a thermal neutron. If tumor cells of a highly malignant glioma (WHO grade III/IV) can be selectively loaded with the currently used boron compound BSH, BNCT is a promising radiation treatment modality eventually resulting in a significantly longer survival time of glioma patients. BNCT is clinically used in Japan for different types of malignant intracranial tumors1. Within the European Collaboration on BNCT for patients suffering from a Glioblastoma multiforme (WHO grade IV). As reported previously by different groups engaged in the European Collaboration2,3,4 we found a consistently high but heterogeneous boron uptake in the tumor tissue of BSH infused glioma patients, whereas normal brain tissue adjacent to the tumor revealed no significant boron uptake’. Taking into account the radiobiological considerations and the characteristics of the epithermal neutron beam which will be used at the Petten Reactor Facility it is incontestable, that the irradiation is more effective if the intracellular boron uptake can be increased. As shown by D. Joel5, the administration of glutathione-monoester (GSH-ME) prior to BSH leads to a higher boron uptake and consequently to a higher radiation damage of colony forming tumor cells derived in vitro from gliosarcoma bearing rats treated with BNCT in vivo. Unfortunately, GSH-ME is not available as a registered drug in Germany. On the other hand, N-acetylcysteine (N-AC) is known to increase significantly the plasma level of glutathione in humans6. N-AC is considered to be a mucoregulatory drug. In addition, N-AC has been found effective to reduce the life-threatening consequences of paracetamol intoxication7 and the toxicity of anti-cancer drugs like cisplatin8. Therefore we have administered N-AC prior to BSH and compared the pharmacokinetics and biodistribution of boron to the continued clinical investigations with BSH alone.
KeywordsMalignant Glioma Glioblastoma Multiforme Glioma Patient Boron Concentration Boron Neutron Capture Therapy
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