Boron neutron capture therapy of a rat glioma

Clendenon, Nancy R.; Barth, Rolf F.; Gordon, Wanda A.; Goodman, Joseph H.; Alam, Ferdous; Staubus, Alfred E.; Boesel, Carl P.; Yates, Allan J.; Moeschberger, Melvin L.; Fairchild, R.G.

doi:10.1097/00006123-199001000-00007

Cited by 25 publications

(6 citation statements)

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“…For the high dose of BSH, the half-times were in reasonably good agreement with the results of Clendenon, et al, 5 also eliminated from the blood in two phases; the slow second elimination phase suggested that there is a depot compartment from which there is slow release back into the blood. The transfer coefficients resulting from the compartment analysis reflected this behavior, and the pattern of uptake in the tumor for BOPP, with a maximum tumor concentration time of 24 hours, further supported this interpretation.…”

Section: Discussionsupporting

confidence: 86%

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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

Ceberg¹,

Brun²,

Kahl³

et al. 1995

Journal of Neurosurgery

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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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Section: Discussionsupporting

confidence: 86%

“…Abe, et al, 2 presented tumor-to-blood ratios mostly below or around unity, in agreement with both the results of Joel, et al, 14 and with this study. The tumor-to-blood ratios reported by Clendenon, et al, 5 were somewhat higher, with a peak value of 5 at 6 hours after the injection.…”

Section: Discussionmentioning

confidence: 71%

A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model

Ceberg¹,

Brun²,

Kahl³

et al. 1995

Journal of Neurosurgery

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“…The morphology of the F98 EGFR glioma was indistinguishable on H&E-stained sections from that of the F98 WT glioma, as was previously described by us [33]. The tumor was composed of a mixed population of spindle shaped cells with fusiform nuclei, frequently forming a whorled pattern of growth, and a smaller subpopulation of polygonal cells with round to oval nuclei.…”

Section: Resultssupporting

confidence: 58%

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors

Yang

Barth

et al. 2009

J Neurooncol

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In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma, designated F98EGFR. EGF was chemically linked to a heavily boronated polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of 125I-labeled or unlabeled BD-EGF (40 μg 10B/10 μg EGF) to F98 glioma bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 μg/g vs. 11.7 μg/g). CED of BD-EGF resulted in a 7.2× increase in the volume of distribution within the infused cerebral hemisphere and a 1.9× increase in tumor uptake of BD-EGF compared with i.t. injection. Based on these favorable bio-distribution data, BNCT was carried out at the Massachusetts Institute of Technology nuclear reactor 14 days following i.c. tumor implantation and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 ± 4.7 days compared to 43.0 ± 2.8 days following i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA), which has been used in both experimental and clinical studies, had a MST of 86.0 ± 28.1 days compared to 39.8 ± 1.6 days for i.v. BPA alone (P < 0.01), 30.9 ± 1.4 days for irradiated controls and 25.1 ± 1.0 days for untreated controls (overall P < 0.0001). These data have demonstrated that the efficacy of BNCT was significantly increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and that the survival data were equivalent to those previously reported by us using the boronated anti-human-EGF mAb, C225 (cetuximab).

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“…Untreated control rats had large (TSI = 3.4) highly invasive tumors that had the characteristic appearance of the F98 glioma (Clendenon et al, 1990). Animals that received 127 I-IUdR alone, administered by Alzet osmotic pumps, generally had smaller tumors (TSI = 2.33), and one out of eight rats was tumor free.…”

Section: Neuropathologic Evaluationmentioning

confidence: 99%

Intracerebral delivery of 5-iodo-2′-deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma

Rousseau

Adam

Deman

et al. 2009

J Synchrotron Radiat

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Iodine-enhanced synchrotron stereotactic radiotherapy takes advantage of the radiation dose-enhancement produced by high-Z elements when irradiated with mono-energetic beams of synchrotron X-rays. In this study it has been investigated whether therapeutic efficacy could be improved using a thymidine analogue, 5-iodo-2'-deoxyuridine (IUdR), as a radiosentizing agent. IUdR was administered intracerebrally over six days to F98 glioma-bearing rats using Alzet osmotic pumps, beginning seven days after tumor implantation. On the 14th day, a single 15 Gy dose of 50 keV synchrotron X-rays was delivered to the brain. Animals were followed until the time of death and the primary endpoints of this study were the mean and median survival times. The median survival times for irradiation alone, chemotherapy alone or their combination were 44, 32 and 46 days, respectively, compared with 24 days for untreated controls. Each treatment alone significantly increased the rats' survival in comparison with the untreated group. Their combination did not, however, significantly improve survival compared with that of X-irradiation alone or chemotherapy alone. Further studies are required to understand why the combination of chemoradiotherapy was no more effective than X-irradiation alone.

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Boron neutron capture therapy of a rat glioma

Cited by 25 publications

References 0 publications

A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model

A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors

Intracerebral delivery of 5-iodo-2′-deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma

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