Time- and dose-related changes in the white matter of the rat brain after single doses of X rays

Calvo, W; Hopewell, J. W.; Reinhold, H; Yeung, T. K.

doi:10.1259/0007-1285-61-731-1043

Cited by 242 publications

(142 citation statements)

References 23 publications

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“…We estimate that the MBs' in-depth integrated dose, assuming an 11% valley dose and a 4.5-cm tissue half-value layer, was 88 Gy. Other investigators exposing the rat brain to a single dose of contiguous unsegmented x-ray beams using a semicircular lead aperture of 10 mm radius found ED 50 values for necrosis in white matter of 23 Gy at 39 weeks and 21 Gy at 52 weeks (33,34). Dividing the 88-Gy integrated dose by the average of these two doses (i.e., 22 Gy), we find a radiation tolerance advantage of 4.0-fold or higher for our beams (because our dose is not for ED 50 ).…”

Section: Discussionmentioning

confidence: 99%

Interlaced x-ray microplanar beams: A radiosurgery approach with clinical potential

Dilmanian

Zhong²,

Bacarian³

et al. 2006

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

176

214

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Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25-to 90-m thick and spaced 100 -300 m on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90°angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 ؋ 3.4 ؋ 3.4 mm 3 exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120-and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-m dose falloff (80 -20%) at the edge of the target, which is much less than the 2-to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.

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Section: Discussionmentioning

confidence: 99%

Interlaced x-ray microplanar beams: A radiosurgery approach with clinical potential

Dilmanian

Zhong²,

Bacarian³

et al. 2006

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

176

214

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“…We conclude that damage to the intestinal microvasculature is not causative in the loss of stem cell function and the eventual depopulation of the intestinal lining that characterizes the GI syndrome. The role of microvascular versus parenchymal cell damage has long been a matter of considerable debate for late effects (15)(16)(17). In recent years, it has become clear that the overall tissue response to radiation damage includes a complex interaction between the different cell types present that begins immediately after the radiation insult and persists throughout the clinically silent period until the expression of the late effect months or even years later.…”

Section: Discussionmentioning

confidence: 99%

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Schuller¹,

Binns

Riley

et al. 2006

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

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The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received wholebody epithermal neutron irradiation at a dose rate of 0.57 ؎ 0.04 Gy⅐min ؊1 . An additional dose was selectively targeted to endothelial cells from the short-ranged (5-9 m) particles released from neutron capture reactions in 10 B confined to the blood by incorporation into liposomes 70 -90 nm in diameter. Different liposome formulations produced 45 ؎ 7 or 118 ؎ 12 g͞g 10 B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ؎ 0.09 or 1.90 ؎ 0.16 Gy⅐min ؊1 , respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2-to 3-fold increased doses to the microvasculature, relative to the nonspecific wholebody neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ؎ 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.gastrointestinal syndrome ͉ boron ͉ liposomes ͉ neutron capture R adiation-induced changes seen in normal tissues are traditionally separated into early and late effects. Stem-cellbased, rapidly renewing normal tissues, such as the bone marrow and the intestinal epithelium, are early responding tissues in which the time courses of the radiation syndromes are directly related to the turnover time of the differentiated functional cell compartments. The intestinal stem cells reside in the crypts of Lieberkühn at the base of the finger-like villi that comprise the intestinal epithelium. Epithelial cells differentiate as they migrate up the crypt and the villus and are eventually sloughed off at the tip into the intestinal lumen: the transit time takes Ϸ3-4

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“…These cells are the primary radiation target in the blood vessel (Calvo et al, 1988), damage to which is responsible for the late radiation effects seen in the CNS after BNC irradiation. The magnitude of the radiation dose from the '0B(n,a)7Li reaction that reaches the nuclei of vascular endothelial cells is dependent on the distribution of a given boron delivery agent.…”

Section: Discussionmentioning

confidence: 99%

Central nervous system tolerance to boron neutron capture therapy with p-boronophenylalanine

Morris

Coderre²,

Micca³

et al. 1997

Br J Cancer

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Summary A rat spinal cord model was used to evaluate the effects of boron neutron capture irradiation on the central nervous system (CNS), using a range of doses of the boron delivery agent pboronophenylalanine (BPA). Three doses of BPA 700, 1000 and 1600 mg kg-' were used to establish the biodistribution of boron-10 ('°B) in blood, spinal cord and brain over a 3-h period after intraperitoneal (ip) administration. At the lowest dose of BPA used, blood '°B levels remained relatively stable over the 3-h sampling period. With the two higher doses of BPA, blood '°B concentrations were greatest at 1 h after BPA administration, and thereafter exhibited a biphasic clearance profile. The largest decline in blood '°B levels occurred between 1 and 2 h after ip injection and was most pronounced (approximately 45%) in the highest BPA dose group. Considered overall, '°B concentrations were marginally lower in the spinal cord than in the brain. Levels of 10B in both of these organs showed a slow but progressive increase with time after administration of BPA. The '°B concentration ratio for blood relative to CNS tissue increased with BPA dosage and reached a peak value of approximately 10:1 in the highest BPA dose group, at 1 h after ip injection. However, at 3 h after injection the 10B concentration ratios had decreased to approximately 3:1 in all of the BPA dose groups. After irradiation with thermal neutrons in combination with BPA at blood '°B concentrations of approximately 42 and approximately 93 gig g-1, myelopathy developed after latent intervals of 20.0 ± 0.6 and 20.0 ± 1.2 weeks respectively. ED50 values (+ s.e.) for the incidence of myelopathy were calculated from probitfitted curves, and were 17.5 ± 0.7 and 25.0 ± 0.6 Gy after irradiation with thermal neutrons at blood '°B levels of approximately 42 and approximately 93,g g-1 respectively. The compound biological effectiveness (CBE) factor values, estimated from these data, were 0.67 ± 0.23 and 0.48 ± 0.18 respectively. This compared with a previous estimate of 0.88 ± 0.14 at a blood '°B concentration of approximately 19 gg g-'. It was concluded that the value of the CBE factor was not influenced by the level of '°B in the blood, but by the blood:CNS '°B concentration ratio. In effect, the CBE factor decreases as the concentration ratio increases. Simulations using boron neutron capture therapy (BNCT) treatment planning software indicate a significant therapeutic advantage could be obtained in moving to higher BPA doses than those in current clinical use.

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Time- and dose-related changes in the white matter of the rat brain after single doses of X rays

Cited by 242 publications

References 23 publications

Interlaced x-ray microplanar beams: A radiosurgery approach with clinical potential

Interlaced x-ray microplanar beams: A radiosurgery approach with clinical potential

Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells

Central nervous system tolerance to boron neutron capture therapy with p-boronophenylalanine

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