CNS Imaging and the Brain Barriers

Sage, Michael R.; Turski, Patrick A.; Levin, Allan B.

doi:10.1007/978-1-4615-7255-8_1

Cited by 7 publications

(1 citation statement)

References 142 publications

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“…n, Number of dogs sampled. mal brain (14). The relatively favorable canine tumor and low normal brain boron concentrations were similar to results of other studies, although strict comparison is difficult due to extensive interstudy variation in compound origin and purity, method of boron analysis, route, dose, timing of administration and sampling, species, and tumor types.…”

Section: Resultssupporting

confidence: 82%

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Kraft¹,

Gavin²,

DeHaan³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Borocaptate sodium (Na2B12HjjSH) is a boron-carrying compound under consideration for use in boron neutron capture therapy. The biodistribution of boron from borocaptate sodium adminition will partly determine boron neutron capture therapy efficacy and normal tissue radiation tolerance. The biodistribution of boron was determined in 30 dogs with spontaneous intracranial tumors at 2, 6, or 12 hr after intravenous borocaptate sodium infusion. Blood and tissue boron concentrations were measured using inductively coupled plasma atomic emission spectroscopy. Mean tumor boron concentration (mean ± standard error) was 35.9 ± 4.6 (n = 15), 22.5 ± 6.0 (n = 9), and 7.0 ± 1.1 jpg of boron per g (a = 6) at 2, 6, and 12 hr, respectively, after borocaptate sodium infusion. Peritumor boron concentrations were elevated above that of normal brain in half of the dogs. Normal brain boron concentration (mean ± standard error) was 4.0 1 0.5, 2.0 ± 0.4, and 2.0 ± 0.3 jg of boron per g at 2, 6, and 12 hr after infusion, respectively. Some cranial and systemic tissues, and blood, had high boron concentration relative to tumor tissue. Geometric dose sparing should partly offset these relatively high normal tissue and blood concentrations. Borocaptate sodium biodistribution is favorable because tumor boron concentrations of recommended magnitude for boron neutron capture therapy were obtained and there was a high tumor-to-normal brain boron concentration ratio.Boron neutron capture therapy (BNCT) is an experimental form of radiation therapy for cancer that results in targeted high linear energy transfer (LET) radiation. BNCT has a number oftheoretical advantages over conventional low LET radiation therapy and has recently been reviewed (1, 2). The localization of a boronated compound within tumor tissue is critical to the success of BNCT, and multiple compounds are under development as potential boron carriers. Promising biodistribution results were obtained with the administration of borocaptate sodium (BSH) in rodents with experimental tumors (3). BSH has low relative toxicity, is available in a standardized form, and has produced favorable results during Japanese clinical trials in humans with malignant brain tumors (4). However, few data are available on biodistribution and pharmacokinetics of BSH, and data are needed prior to approval of human pharmacokinetic trials in the United States. Studies using dogs with spontaneous brain tumors were performed to evaluate the relative biodistribution of BSH and potential implications for use of BSH for BNCT are discussed.MATERIALS AND METHODS Dogs with spontaneous intracranial tumors were referred by regional veterinary practitioners. Diagnosis of intracranial tumors was based on results of pre-and post-contrast magnetic resonance imaging and computed tomography of the brain. BSH (natural isotopic ratio: 80% 11B, 20% 10B; Callery Chemical, Pittsburgh) was administered intravenously at 55 mg of boron per kg of body weight dissolved in 11 ml of physiological saline per kg ofbody weight ...

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Section: Resultssupporting

confidence: 82%

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Kraft¹,

Gavin²,

DeHaan³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Neurotoxicity

Leonardi¹,

Agati²

1999

Trends in Contrast Media

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Mechanisms of blood-brain barrier breakdown

Greenwood¹

1991

Neuroradiology

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The functional status of the blood-brain barrier (BBB) must be taken into account when designing and interpreting brain imaging techniques. The integrity of the BBB is affected in many diseases of the brain, with the potential involvement of a number of different but poorly understood cellular mechanisms. Factors known to disrupt the BBB experimentally include arachidonic acid and the eicosanoids, bradykinin, histamine and free radicals. These active compounds, released in pathological tissue, may alter cytosolic calcium levels and induce second messenger systems leading to an alteration in BBB permeability. Extravasation of plasma proteins may occur via disrupted tight junctions, stimulation of fluid-phase vesicular transport or the formation of transcellular pores or channels.

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CNS Imaging and the Brain Barriers

Cited by 7 publications

References 142 publications

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Neurotoxicity

Mechanisms of blood-brain barrier breakdown

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