Pathological study of eight patients with glioblastoma multiforme treated by neutroncapture therapy using boron 10

Godwin, John T.; Farr, Lee E.; Sweet, William H.; Robertson, James S.

doi:10.1002/1097-0142(1955)8:3<601::aid-cncr2820080326>3.0.co;2-r

Cited by 98 publications

(33 citation statements)

References 22 publications

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“…Boron neutron capture therapy (BNCT) of cancer depends on the selective targeting of sufficient quantities of boron-10 (approximately 30 µg/g of tumor) to the tumor cells for effective killing via the boron neutron capture fission reaction (Sweet 1997; Godwin et al, 1955). Since the lethal reaction produced in BNCT is limited to a range of less than a single cell diameter, BNCT is potentially capable of killing individual cancer cells while sparing the neighboring normal cells.…”

Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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There is a pressing need for new and more efficient boron delivery agents to tumor cells for use in boron neutron capture therapy (BNCT). A class of boronated unnatural cyclic amino acids has demonstrated a remarkable selectivity toward tumors in animal and cell culture models, far superior to currently used agents in clinical BNCT. One of these amino acids, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC), has shown a tumor to blood ratio of 8 and a tumor to normal brain ratio of nearly 21 in a melanoma bearing mouse model. This work represents further biological characterization of this compound for tumor targeting in an EMT6 murine mammary carcinoma mouse model and a T98G human glioblastoma cell line. Female BALB/c mice bearing EMT6 tumors were injected with the fructose complex form of racemic mixtures of cis-and trans isomers of ABCPC in identical concentrations. Boron concentrations were measured in the tumor, blood, brain, skin, and liver tissues at 1, 3, and 5 hr post injection. These observations revealed a remarkable difference in racemic mixtures of cis and trans isomers in tumor targeting by boron. This implies that further separation of the L and D forms of this compound may enhance tumor targeting to an even higher degree than that provided by the racemic mixtures. Since the uptake measurements were made in homogenized tumor and normal tissues, little is known about the subcellular location of the boron arising from the various isomeric forms of the amino acid. To study subcellular delivery of boron from ABCPC in T98G human glioblastoma cells, we employed secondary ion mass spectrometry (SIMS) based technique of ion microscopy, which is capable of quantitatively imaging isotopic (elemental) gradients in cells and tissues at 500 nm spatial resolution. The T98G cells were exposed to the nutrient medium containing 100 ppm boron equivalent of a mixture of both L and D isomers of ABCPC in the form of a fructose complex for 1 hr. Following this treatment, the cells were fast frozen, freeze-fractured, and freeze-dried for SIMS analysis. Within an hour of exposure, ABCPC provided partitioning of intracellular to extracellular boron of 3/1. SIMS imaging revealed that boron from ABCPC was distributed throughout the cell, including the nucleus. This level of boron delivery within an hour of exposure is superior to p-boronophenylalanine (BPA) and sodium borocaptate (BSH), which have been previously studied by SIMS in the same cell line. These encouraging observations provide compelling support for further isomeric separations of ABCPC into the D and L forms for enhanced tumor targeting and continued testing of these compounds as new boron carriers in BNCT.

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Section: Introductionmentioning

confidence: 99%

Biological evaluation of boronated unnatural amino acids as new boron carriers

Kabalka

Yao

Marepally

et al. 2009

Applied Radiation and Isotopes

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“…The principle of neutron capture therapy (NCT) utilizes the properties of thermal neutrons. Neutron capture therapy was proposed (Locher, 1936) within 4 years of the discovery of the neutron, although no clinical trials were attempted until 1952 (Godwin et al, 1955); like the first trials of fast neutron therapy, these proved unsuccessful.…”

Section: Boron Neutron Capture Therapymentioning

confidence: 99%

“…Following experimental work in animals using various boron and lithium compounds in the 1940s, clinical trials using BNCT commenced in the 1950s at Brookhaven National Laboratory, USA (Godwin et al, 1955) and later at Massachusetts General Hospital, USA (Asbury et al, 1972). These trials used watersoluble boron compounds (which did not localize in the tumour, although they were excluded from normal brain) and thermal neutrons (which are rapidly attenuated in tissue).…”

Section: The History Of Bnctmentioning

confidence: 99%

A review of boron neutron capture therapy (BNCT) and the design and dosimetry of a high-intensity, 24 keV, neutron beam for BNCT research

Perks

Mill²,

Constantine³

et al. 1988

The British Journal of Radiology

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This paper reviews the development of boron neutron capture therapy (BNCT) and describes the design and dosimetry of an intermediate energy neutron beam, developed at the Harwell Laboratory, principally for BNCT research. Boron neutron capture therapy is a technique for the treatment of gliomas (a fatal form of brain tumour). The technique involves preferentially attaching 10B atoms to tumour cells and irradiating them with thermal neutrons. The thermal neutron capture products of 10B are short range and highly damaging, so they kill the tumour cells, but healthy tissue is relatively undamaged. Early trials required extensive neurosurgery to exposure the tumour to the thermal neutrons used and were unsuccessful. It is thought that intermediate-energy neutrons will overcome many of the problems encountered in the early trials, because they have greater penetration prior to thermalization, so that surgery will not be required. An intermediate-energy neutron beam has been developed at the Harwell Laboratory for research into BNCT. Neutrons from the core of a high-flux nuclear reactor are filtered with a combination of iron, aluminium and sulphur. Dosimetry measurements have been made to determine the neutron and gamma-ray characteristics of this beam, and to monitor them throughout the four cycles used for BNCT research. The beam is of high intensity (approximately 2 x 10(7) neutrons cm-2 s-1, equivalent to a neutron kerma rate in water of 205 mGy h-1) and nearly monoenergetic (93% of the neutrons have energies approximately 24 keV, corresponding to 79% of the neutron kerma rate).

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“…11 While these substances were found to be well tolerated by patients, the trails were not successful. 11 The main reasons were that the thermal neutron beam was too weak and the compounds did not preferentially locate in the tumor and that the boron agents were not tumor specific. Since that time, a variety of different carrier molecules have been investigated as possible boron delivery agents to tumor cells.…”

Section: Introductionmentioning

confidence: 99%