Glioblastoma, brain metastases and soft tissue sarcoma of extremities: candidate tumors for BNCT.

(10)B-concentration ratios between human glioblastoma multiforme (U87MG), sarcoma (S3) and melanoma (MV3) xenografted in nu/nu mice and selected normal tissues were investigated to test for preferential (10)B-accumulation. Animals received BSH, BPA or both compounds sequentially. Mean (10)B-concentration ratios between tumor and normal tissues above 2 were found indicating therapeutic ratios. In addition to glioblastoma, brain metastases and soft tissue sarcoma appear to be promising targets for future BNCT research.

Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT).

The first BNCT trials took place in the USA in the early 1960's, yet BNCT is still far from mainstream medicine. Nonetheless, in recent years, reported results in the treatment of head and neck cancer and recurrent glioma, coupled with the progress in developing linear accelerators specifically for BNCT applications, have given some optimism to the future of BNCT. This article provides a brief reminder on the ups and downs of the history of BNCT and supports the view that controlled and prospective clinical trials with a modern design will make BNCT an evidence-based treatment modality within the coming decade.

Biodistribution of (10)B for Boron Neutron Capture Therapy (BNCT) in a mouse model after injection of sodium mercaptoundecahydro-closo-dodecaborate and l-para-boronophenylalanine.

In boron neutron capture therapy, the absorbed dose from the (10)B(n,alpha)(7)Li reaction depends on the (10)B concentration and (10)B distribution in the irradiated volume. Thus compounds used in BNCT should have tumor-specific uptake and low accumulation in normal tissues. This study compares in a mouse model the (10)B uptake in different organs as delivered by l-para-boronophenylalanine (BPA, 700 mg/kg body weight, i.p.) and/or sodium mercaptoundecahydro-closo-dodecaborate (BSH, 200 mg/kg body weight, i.p). After BSH injection, the (10)B concentration was high in kidneys (20 +/- 12 microg/g) and liver (20 +/- 12 microg/g) but was low in brain (1.0 +/- 0.8 microg/g) and muscle (1.9 +/- 1.2 microg/g). After BPA injection, the (10)B concentration was high in kidneys (38 +/- 25 microg/g) and spleen (17 +/- 8 microg/g) but low in brain (5 +/- 3 microg/g). After combined BPA and BSH injection, the effect on the absolute (10)B concentration was additive in all organs. The ratio of the (10)B concentrations in tissues and blood differed significantly for the two compounds depending on the compound combination, which implies a different uptake profile for normal organs.

Laser postionization secondary neutral mass spectrometry in tissue: a powerful tool for elemental and molecular imaging in the development of targeted drugs.

The exact intracellular localization and distribution of molecules and elements becomes increasingly important for the development of targeted therapies and contrast agents. We show that laser postionization secondary neutral mass spectrometry (laser-SNMS) is well suited to localize particular elements and small molecules with subcellular spatial resolution applying the technique exemplary to Boron Neutron Capture Therapy (BNCT). We showed in a murine sarcoma that the drugs used for clinical BNCT, namely l-para-boronophenylalanine (700 mg/kg body weight i.p.) and sodium mercaptoundecahydro-closo-dodecaborate (200 mg/kg body weight i.p.), transport the therapeutic agent (10)B into the cytoplasm and into the nucleus itself, the most sensitive area of the cell. Sodium mercaptoundecahydro-closo-dodecaborate distributes (10)B homogeneously and l-para-boronophenylalanine heterogeneously. When combining laser-SNMS with prompt gamma-ray analysis as a screening technique, strategies for BNCT can be elaborated to develop new drugs or to improve the use of existing drugs on scientifically based evidence. The study shows the power of laser-SNMS in the early stages of drug development, also outside BNCT.

Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT).

Boron Neutron Capture Therapy (BNCT) is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having a high biological effectiveness and a very short range in tissue, being limited to approximately one cell diameter. This opens the possibility for a highly selective cancer therapy. BNCT strongly depends on the selective uptake of 10B in tumor cells and on its distribution inside the cells. The chemical properties of boron and the need to discriminate different isotopes make the investigation of the concentration and distribution of 10B a challenging task. The most advanced techniques to measure and image boron are described, both invasive and non-invasive. The most promising approach for further investigation will be the complementary use of the different techniques to obtain the information that is mandatory for the future of this innovative treatment modality.

Neutron activation of patients following boron neutron capture therapy of brain tumors at the high flux reactor (HFR) Petten (EORTC Trials 11961 and 11011).

BACKGROUND AND PURPOSE: At the High Flux Reactor (HFR), Petten, The Netherlands, EORTC clinical trials of Boron Neutron Capture Therapy (BNCT) have been in progress since 1997. BNCT involves the irradiation of cancer patients by a beam of neutrons, with an energy range of predominantly 1 eV to 10 keV. The patient is infused with a tumor-seeking, (10)B-loaded compound prior to irradiation. Neutron capture in the (10)B atoms results in a high local radiation dose to the tumor cells, whilst sparing the healthy tissue. Neutron capture, however, also occurs in other atoms naturally present in tissue, sometimes resulting in radionuclides that will be present after treatment. The patient is therefore, following BNCT, radioactive. The importance of this induced activity with respect to the absorbed dose in the patient as well as to the radiation exposure of the staff has been investigated. MATERIAL AND METHODS: As a standard radiation protection procedure, the ambient dose equivalent rate was measured on all patients following BNCT using a dose ratemeter. Furthermore, some of the patients underwent measurements using a gamma-ray spectrometer to identify which elements and confirm which isotopes are activated. RESULTS: Peak levels, i.e., at contact and directly after irradiation, are of the order of 40-60 muSv/h, falling to < 10 muSv/h 30-50 min after treatment. The average ambient dose equivalent in the first 2 h at a distance of 2 m from the patient is in the order of 2.5 muSv. The ambient dose equivalent rate in 2 m distance from the patient's head at the earliest time of leaving the reactor center (20 min after the end of treatment) is far less than 1 muSv/h. The main radioisotopes were identified as (38)Cl, (49)Ca, and (24)Na. Furthermore, in two patients, the isotopes (198)Au and (116m)In were also present. The initial activity is predominantly due to (49)Ca, whilst the remaining activity is predominantly due to (24)Na. CONCLUSION: The absorbed dose resulting from the activated isotopes in the irradiated volume is in the order of < 1% of the prescribed dose and therefore does not add a significant contribution to the absorbed dose in the target volume. In other parts of the patient's body, the absorbed dose by induced activity is magnitudes smaller and can be neglected. The levels of radiation received by staff members and non-radiation workers (i.e., accompanying persons) are well below the recommended limits.