| 1. |
- Ceberg, Crister, et al.
(författare)
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A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model
- 1995
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.
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| 2. |
- Ceberg, Crister, et al.
(författare)
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A stochastic model for subcellular dosimetry in boron neutron capture therapy
- 1995
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 40:11, s. 1819-1830
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic effectiveness of boron neutron capture therapy is highly dependent on the microscopic distribution of the administered boron compound. Two boron compounds with different uptake mechanisms in the tumour cells may thus cause effects of different degrees even if the macroscopic boron concentrations in the tumour tissue are the same. This difference is normally expressed quantitatively by the so-called relative local efficiency (RLE). In this work, a stochastic model for the subcellular dosimetry has been developed. This model can be used to calculate the probability for an energy deposition above a certain threshold level in the cell nucleus due to a single neutron capture reaction. If a threshold cell-kill function is assumed, and if the dose is low enough that multiple energy depositions are rare, the model can also be applied to calculations of the survival probability for a cell population. Subcellular boron distributions in rats carrying RG 2 rat gliomas were measured by subcellular fractionation after administration of two different boron compounds: a sulphydryl boron hydride (BSH) and a boronated porphyrin (BOPP). Based on these data, the RLE factors were then calculated for these compounds using the stochastic model.
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| 3. |
- Ceberg, Crister, et al.
(författare)
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Neutron capture imaging of 10B in tissue specimens
- 1993
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Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 26:2, s. 139-146
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Tidskriftsartikel (refereegranskat)abstract
- Boron Neutron Capture Therapy (BNCT) is an attractive concept for radiation treatment of malignant tumours. The patients receive a 10B-carrying compound with selective uptake in tumour cells, after which they are irradiated with epithermal neutrons. Theoretically, the tumour cells are killed by the high-LET particles produces in 10B(n, alpha)7Li reactions inside or close to the cell nucleus, while healthy brain cells with no boron uptake will be spared. In practice, a successful BNCT depends on the actual boron-distribution in the tissue, and consequently a new boron-compound aimed for BNCT must undergo detailed bio-distribution studies before clinical trials. In experimental work there is accordingly a great need for methods for quantitative bio-distribution measurements in tissue samples. In this paper we present an improved technique for neutron activated autoradiography providing quantitative boron images of freeze-sectioned tissue specimens from highly malignant rat brain gliomas. Particular attention has been paid to the correlation with the morphology of the specimens and to the altered self-absorption properties due to freeze-drying. A self-absorption correction factor for tumour tissue has been experimentally determined.
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| 4. |
- Ceberg, Crister, et al.
(författare)
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Performance of sulfhydryl boron hydride in patients with grade III and IV astrocytoma: a basis for boron neutron capture therapy
- 1995
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Ljunggren, Kaj, et al.
(författare)
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Beta camera low activity tumor imaging
- 1993
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 32:7-8, s. 869-872
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Tidskriftsartikel (refereegranskat)abstract
- A new technique, the beta camera, to complement film autoradiography, with fast quantitative imaging of beta particle-emitting radionuclides has been developed. It consists of a thin plastic scintillator and a light-sensitive microchannel plate detector. The thin tissue sample is mounted on the scintillator. Our first system had a high background and a moderate spatial resolution of 900 microns. We now report an improved system with a photomultiplier tube mounted on the scintillator of the microchannel plate detector. Only events registered by both detectors are accepted. A fast coincidence unit processes the signals, and if a time overlap exists, an event is generated in the beta camera. In the coincidence mode, images with low activity distribution of 201Tl (count rate 1 s-1) in 50 microns-thick slices of a human glioma tumor could be recorded with a spatial resolution of 500 microns.
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| 6. |
- Salford, Leif, et al.
(författare)
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A new brain tumour therapy combining bleomycin with in vivo electropermeabilization
- 1993
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 194:2, s. 938-943
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Tidskriftsartikel (refereegranskat)abstract
- The potentials of in vivo electropermeabilization in combination with bleomycin in brain tumor treatment have been explored. In the brain of normal Fischer 344 rats, 2 electrodes were placed 5 mm apart. Electropermeabilization was performed with 8 to 12 exponential 400 V pulses with a time constant of 325 microseconds. Some animals were given bleomycin i.v., 1mg/kg b.w., 4 minutes before electric pulses delivery. No adverse effects were recorded during the observation of the animals during the following month. The effect of bleomycin and electropermeabilization upon tumour growth was studied in rats with glioma cells (RG2) implanted in the head of the right caudate nucleus. Treatment was given at different time intervals after the implantation of tumor cells and the effect upon survival was studied. Bleomycin alone did not prolong the survival of the animals. On the contrary, bleomycin plus electropermeabilization on the 10th, 11th or 12th day after inoculation increased the survival time to almost double that of untreated animals. We conclude that this treatment may be of value in brain tumour therapy.
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| 7. |
- Sjöholm, H, et al.
(författare)
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Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat
- 1995
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Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 6:1, s. 109-114
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.
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