boron and Astrocytoma

To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes.. Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of (18)F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. (11)C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET.. PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other.. T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

Topics: Algorithms; Astrocytoma; Boron; Boron Compounds; Boron Neutron Capture Therapy; Brain Neoplasms; Carbon Radioisotopes; Glioblastoma; Glioma; Humans; Methionine; Phenylalanine; Positron-Emission Tomography; Radiation-Sensitizing Agents; Radiotherapy Planning, Computer-Assisted

This study investigated the rationale of boron neutron capture therapy (BNCT) for the treatment of Grade III and IV astrocytoma. The European Community joint research program on BNCT plans to use sulfhydryl boron hydride (BSH) in clinical trials. The work presented here, examines the performance of BSH in eight patients with Grade III and IV astrocytoma using a measurement technique which precisely correlates the boron uptake with the histology of the tumor and the peritumoral brain. Astrocytomas are exceptionally heterogeneous and spread migrating tumor cells into the surrounding brain. The patients were infused with 50 mg BSH per kilogram of body weight at 12, 18, 24 or 48 hours before surgery. At the time of operation, specimens were obtained of the tumor, skin, muscle, dura, blood, urine, and, when surgically possible, the brain adjacent to tumor. In three patients the intracellular boron distribution was investigated by subcellular fractionation. The blood clearance was biphasic with half-lives of 0.6 and 8.2 hours. After 3 days, approximately 70% of the dose injected was excreted in the urine. The maximum boron concentration in the tumor was 20 ppm, 12 hours after the infusion. The tumor-to-blood ratios ranged between 0.2 and 1.4, with the highest values after 18 to 24 hours. In the brain specimens the boron concentration never exceeded 1 ppm. This work confirms a selective uptake of boron in the tumor compared to the surrounding brain and that boron, to some extent, is incorporated in the tumor cells.

Topics: Astrocytoma; Biopsy; Body Fluid Compartments; Borohydrides; Boron; Boron Neutron Capture Therapy; Brain; Brain Neoplasms; Half-Life; Humans; Least-Squares Analysis; Sulfhydryl Compounds; Tissue Distribution; Tomography, X-Ray Computed

If a sufficient concentration of the stable isotope 10B is introduced into a neoplasm, radiation therapy can be effected by short-range heavy charged particles from the disintegration of 10B by slow neutrons. Brain tumors were irradiated postoperatively by Hatanaka and co-workers in Japan using a 1 to 2 hour intraarterial infusion of 10B-enriched Na2B12H11SH (Na210B12H11SH) before exposure of the tumor-bearing area of the brain to slow neutrons from a 100 kilowatt nuclear reactor. The clinical outcome of such boron neutron capture therapy has been favorably impressive in some patients, but its efficacy in brain tumors needs improvement. In our study, a terminally ill patient with malignant astrocytoma was infused intravenously with Na210B12H11SH for 25 hours. The postmortem distribution of 10B in unfixed, frozen, tumor-bearing brain and spinal cord tissues was studied by comparing representative cryostat sections of these specimens with neutron-induced heavy charged particle radiographs of the same sections. Preferential accumulation of 10B was observed in the tumor, with relatively little accumulation of 10B in the parenchyma of the central nervous system.

Topics: Animals; Astrocytoma; Borohydrides; Boron; Brain Neoplasms; Humans; Isotopes; Mice; Radiotherapy; Sulfhydryl Compounds

Boron-neutron capture therapy (BNCT) is theoretically a highly selective treatment of infiltrating tumours, in that the tumoricidal heavy particle radiation is limited to a sphere of 10 microns around a tumour cell which is loaded with non-radioactive boron-10 atoms. There were 73 gliomas among the 83 cases treated by boron-neutron capture therapy. For grade III-IV cerebral gliomas, 5 and 10 year survival rates were an unimpressive 19 and 10% respectively. This was the result of technical problems such as unsatisfactory reactors and inadequate craniotomies for the majority of the patients. If the analysis was limited to those whose tumours had been irradiated with more than 2.5 x 10(12) neutrons/cm2 (yielding more than 3,000 rem or more), the 5 and 10 year survival were almost 100 and 50%. The longest surviving glioblastoma (grade IV) patient has lived in a satisfactory manner for the past 15 years. For the cases who had been treated with borderline doses (lethal or sublethal), interpretation of the postoperative CTs was frequently intriguing. Several cases had to undergo re-opening and occasionally even another BNCT, only to find no viable tumour tissue. Death occurred in some, either due to discontinuation of supportive treatments by local physicians, or due to excessive therapies by the author directly involved in the patient's care, both of whom had erroneously believed in recurrence. At autopsy, residual tumour cells were recognized only in the areas where the above-mentioned neutron fluence had not been delivered at the time of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Astrocytoma; Boron; Brain Neoplasms; Glioma; Humans; Isotopes; Male; Neutrons; Postoperative Complications; Tomography, X-Ray Computed

Topics: Adult; Alpha Particles; Animals; Astrocytoma; Autoradiography; Boron; Brain Neoplasms; Cats; Child; Cobalt Radioisotopes; Female; Frontal Lobe; Glioblastoma; Glioma; Humans; Male; Methods; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Middle Aged; Neutrons; Pons

Topics: Adolescent; Adult; Astrocytoma; Boron; Brain Neoplasms; Female; Frontal Lobe; Glioblastoma; Humans; Male; Melanoma; Middle Aged; Neutrons; Occipital Lobe; Parietal Lobe; Radiation Injuries; Radioisotopes; Radiotherapy Dosage; Spinal Cord; Temporal Lobe