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Measurements and calculations of thermal neutron fluence rate and neutron energy spectra resulting from moderation of 252Cf fast neutrons: applications for neutron capture therapy.

252Cf is a neutron emitting radioisotope which has promise for both standard brachytherapy and neutron capture enhanced brachytherapy. In this study, experimental measurements and calculations were used to determine the thermal neutron fluence rate, phi(th) [n cm(-2) s(-1) mg(-1)], in the vicinity of 252Cf applicator tube (AT) type sources. Results of these measurements were confirmed with Monte Carlo calculations performed in a distributed manner on multiple workstations using MCNP. Three studies were executed: (1) relative phi(th) as a function of distance from a 252Cf AT source in an A-150 tissue equivalent plastic phantom using thermoluminescent dosimeters (TLDs) of varying 6Li/Li enrichment, (2) phi(th) measured with gold foils in a 114 liter water phantom 5 cm from two 252Cf AT sources, and (3) calculations of the impact of phantom material composition (e.g., A-150, water, brain, muscle) on phi(th) from moderated 252Cf fast neutrons. TLD results and Monte Carlo calculations in A-150 of relative phi(th) typically agreed within 1% and at most differed by 3% for distances from 1 to 6 cm. Foil measurements followed the ASTM E 262-86e protocol, and the ratio of activated plain and Cd encased gold foils (7.31) agreed well with the calculated ratio (7.26). Measured phi(th) at 5 cm (1.70+/-0.10 x 10(7) n cm(-2) s(-1) mg(-1)) was 10% greater than that determined using MCNP (1.55+/-0.12 x 10(7) n cm(-2) s(-1) mg(-1)), but was within the combined uncertainties. Compared with A-150 at a distance of 1 cm, phi(th) was 20%, 22%, and 32% less for water, brain, and muscle, respectively; these ratios decreased to 16%, 16%, and 24% less, respectively, at a distance of 5 cm from the source in a 15 cm diameter phantom. Comparisons of these results generally agreed with those in the literature for a value of 2 x 10(7) n cm(-2) s(-1) mg(-1) in water at 3 cm.

Algorithms↗

Control of intracerebral gliosarcomas in rats by boron neutron capture therapy with p-boronophenylalanine.

Boron neutron capture therapy (BNCT) of transplanted intracerebral GS-9L rat gliosarcomas was effected by irradiation at a nuclear reactor, primarily with thermal neutrons, after two intragastric doses of p-boronophenylalanine (BPA). At the time of BNCT, tumor 10B levels were approximately 40 micrograms 10B/g with tumor:blood and tumor:brain 10B concentration ratios of about 3.3:1 and 3.9:1, respectively. This resulted in calculated doses to tumor that were approximately 2.3-fold greater than those to normal brain parenchyma and brain vascular endothelium within the treatment volume. Approximately 75% of the tumor dose resulted from the 10B(n,alpha)7Li nuclear reaction. The median survival of untreated rats (n = 20) was 20 days after initiation of tumors. Reactor irradiation only (no BPA) increased the median survival to 25 days (n = 25). None of the rats in the untreated or irradiation-only groups survived longer than 34 days after initiation of tumors. Two BNCT dose levels were used: 8.9 Gy (19.3 Gy x relative biological effectiveness, or Gy-eq) and 13.4 Gy (29.0 Gy-eq). The median post-BNCT survivals of BPA-treated rats in the 8.9-Gy (n = 16) and 13.4-Gy (n = 12) groups were 60 and 120 days, respectively, including seven long-term (greater than 12 months) survivors at 8.9 Gy and six long-term (greater than 5 months) survivors at 13.4 Gy. Survival times following BPA-based BNCT (either 8.9 or 13.4 Gy) were significantly longer than those following 250-kVp X-ray doses of 15 Gy (n = 24), 22.5 Gy (n = 32) or 30 Gy (n = 26).

Animals↗

Boron neutron capture therapy of a murine melanoma.

Boron neutron capture therapy has been carried out on BALB/c mice carrying the Harding-Passey melanoma s.c. on the thigh. p-Boronophenylalanine (BPA), a boronated analogue of natural melanin precursors, was used to target boron selectively to melanoma. BPA was administered to the mice either via i.p. injection or p.o. by intubation. 10B concentrations in tumor ranged from 15 to 40 ppm depending on the route and timing of administration. Irradiations with a predominantly thermal neutron beam were performed at the Brookhaven Medical Research Reactor. In the absence of BPA, only transient tumor growth delays were observed at low neutron fluences. At 5 x 10(16) n/m2, 4 of 22 tumors irradiated in the absence of BPA underwent long-term tumor growth control; after p.o. administration of BPA (40 ppm 10B in the tumor), the fraction of tumors controlled increased to 11 of 19. The average dose to the tumor in the latter group was 17.8 Gy, of which 14.8 Gy were due to the 10B neutron capture reaction. The biological effectiveness of the absorbed dose from the neutron capture reaction, at the 50% tumor control level, was found to be twice that of 100 kVp X-rays.

Animals↗

Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.

Brachytherapy↗

The EORTC Boron Neutron Capture Therapy (BNCT) Group: achievements and future projects.

Boron Neutron Capture Therapy (BNCT) is an experimental treatment modality that takes place in a nuclear research reactor. To progress from preclinical studies to patient treatment is a challenge requiring strict quality management and special solutions to licensing, liability, insurance, responsibility and logistics. The European Organisation for the Research and Treatment of Cancer (EORTC) BNCT group has started the first European clinical trial of BNCT for glioblastoma patients at the European High Flux Reactor (HFR) in Petten, The Netherlands, conducted by the Department of Radiotherapy of the University of Essen, Germany. A very strict quality management had to be installed following the European rules on safety and quality assurance for nuclear research reactors, for radioprotection, for radiotherapy and for clinical trials. The EORTC BNCT Group has created a virtual European-wide hospital to handle the complex management of patients treated with BNCT. New clinical trials are currently under development.

Boron Neutron Capture Therapy↗

Neutron induced brachytherapy: a combination of neutron capture therapy and brachytherapy.

Brachytherapy is a widely used radiation therapy modality while neutron capture therapy is being intensely studied. These methods provide some advantages, but also have limitations that might be ameliorated by combining them. A technique that uses stable solid seeds or needles of Gd which are irradiated in vivo with neutrons has been evaluated. Monte Carlo calculations show that 5000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm3 with a three-plane implant of 9-Gd needles. The tumor to normal tissue advantage of this method is as good as brachytherapy using 60Co seeds. Measurements of prompt gamma dose with films and TLD-700s in a lucite phantom verify the Monte Carlo evaluation. Dose measurements of a Gd needle in air also show that Gd is promising for this form of brachytherapy.

Brachytherapy↗

Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages.

OBJECT: To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds-sodium borocaptate (BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. METHODS: Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. CONCLUSIONS: This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

Adult↗

Boron neutron capture therapy for cancer. Realities and prospects.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.

Boron Neutron Capture Therapy↗

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors.

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described.

Boron↗

The equal effectiveness ratio: a quantitative approach to the evaluation of compounds for boron neutron capture therapy.

The resurgence of interest in boron neutron capture therapy (BNCT) as a potential treatment for glioblastomas and melanomas has resulted in a quest to identify and synthesize candidate compounds which can physiologically target the 10B atoms to tumor cells. Numerous boron-carrying compounds are now available and awaiting evaluation. Because the products of the boron neutron capture (BNC) reaction generally contribute greater than 50% of the dose in BNCT, the evaluation of the efficacy of boron compounds would be more precise if it were possible to remove, quantitatively, the dose contributed by the external reactor radiations. The purpose of this study is to report a method which does just that, i.e., leaves for precise evaluation the biological effect that is ascribable to the BNC products only. The evaluation involves a series of separately quantifiable factors, the product of which provides an overall "figure of merit" for the compound.

Animals↗

[Superimposition alpha-autoradiography for basic study of neutron capture therapy (author's transl)].

Since Locher suggested the possibility of neutron capture therapy, a number of investigators have been making efforts to establish clinical application of this treatment. For success of this therapy one of the keys is to develop a proper boron compound with selective accumulation and high concentration in the tumor. So far, sodium mercaptoundecahydrododecaborate, Na2B12H11SH is the best candidate for this purpose with its high concentration and selectivity shown by chemical analysis. Nevertheless, histological study of boron uptake to know fine distribution in tissue is inevitable for evidence of effectiveness of clinical therapy. Cytological effects in neutron capture therapy largely depend on close association of B-10 with the tumor cell. B-10, being non-radioactive isotope, can not be used as a tracer for autoradiographical study of boron distribution in tissue. Instead, alpha particles produced by (n, alpha) reaction can be used for autoradiography which demonstrates not only location of boron in tissue but tracks by alpha particles expected to occur in actual neutron irradiation. Dielectric organic polymer has been calling attention for its ability to register heavy particles which was utilized for alpha autoradiography. Autoradiography by use of plastic film without nuclear emulsion has advantages; (1) simple procedures, (2) no darkroom needed, (3) a lower background obtainable, (4) little influence of temperature and moisture, (5) long standing material and so on. The disadvantage of this procedure is that tissue sections are easily damaged by strong alkalinity used for chemical etching. To solve this problem an overlapping histologic technique was worked out, permitting one to determine the relation of the heavy particle tracks to the intra and extracellular structures. Na2B12H11SH, a boron compound already in practical use, has been restudied by using this new technique. Autoradiograms showed favorable results with abundant alpha tracks over the tumor tissue in close relation to the cells and with very few tracks over the normal brain parenchyma. This technique is a useful means not only for further development of boron compounds but for other alpha emitters.

Animals↗

The compound factor of the 10B(n,alpha)7Li reaction from borocaptate sodium and the relative biological effectiveness of recoil protons for induction of brain damage in boron neutron capture therapy.

To make clinical trials of boron neutron capture therapy safe for patients, it is necessary to know the relative biological effectiveness (RBE) of the radiation components and the compound factor of the boron carrier to be used. Here a method is derived to determine the RBE of recoil protons and the compound factor of compounds from in vivo experiments with different concentrations of boron. The method uses a simultaneous fit of both these parameters to all experimental data. This method is applied to the studies of tolerance of healthy tissue in dogs at the High Flux Reactor in Petten, The Netherlands. The RBE for the recoil protons generated by the neutrons present in the epithermal neutron beam [together with the RBE of the protons from the 14N(n,p)14C reaction] for induction of severe neurological symptoms was found to be 3.93+/-0.43 (95% confidence limits 3.06-4.79), and 2.33+/-0.14 (2.04-2.61) for induction of changes detectable by magnetic resonance imaging. The compound factor for Na2B12H11SH in brain tissue, using severe neurological symptoms as end point, was determined to be 0.37+/-0.06 (95% confidence limits 0.24-0.50). For changes detectable by magnetic resonance imaging, the value was found to be 0.65+/-0.04 (0.58-0.73).

Animals↗

Synthesis and biological evaluation of folate receptor-targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy.

Successful treatment of cancer by boron neutron capture therapy (BNCT) requires the selective delivery of (10)B to constituent cells within a tumor. The expression of the folate receptor is amplified in a variety of human tumors and potentially might serve as a molecular target for BNCT. In the present study we have investigated the possibility of targeting the folate receptor on cancer cells using folic acid conjugates of boronated poly(ethylene glycol) (PEG) containing 3rd generation polyamidoamine dendrimers to obtain (10)B concentrations necessary for BNCT by reducing the uptake of these conjugates by the reticuloendothelial system. First we covalently attached 12-15 decaborate clusters to 3rd generation polyamidoamine dendrimers. Varying quantities of PEG units with varying chain lengths were then linked to these boronated dendrimers to reduce hepatic uptake. Among all prepared combinations, boronated dendrimers with 1-1.5 PEG(2000) units exhibited the lowest hepatic uptake in C57BL/6 mice (7.2-7.7% injected dose (ID)/g liver). Thus, two folate receptor-targeted boronated 3rd generation polyamidoamine dendrimers were prepared, one containing approximately 15 decaborate clusters and approximately 1 PEG(2000) unit with folic acid attached to the distal end, the other containing approximately 13 decaborate clusters, approximately 1 PEG(2000) unit, and approximately 1 PEG(800) unit with folic acid attached to the distal end. In vitro studies using folate receptor (+) KB cells demonstrated receptor-dependent uptake of the latter conjugate. Biodistribution studies with this conjugate in C57BL/6 mice bearing folate receptor (+) murine 24JK-FBP sarcomas resulted in selective tumor uptake (6.0% ID/g tumor), but also high hepatic (38.8% ID/g) and renal (62.8% ID/g) uptake, indicating that attachment of a second PEG unit and/or folic acid may adversely affect the pharmacodynamics of this conjugate.

Animals↗

Development and in vitro studies of epidermal growth factor-dextran conjugates for boron neutron capture therapy.

A delivery molecule for directed boron neutron capture therapy against epidermal growth factor (EGF) receptor-rich tumors, such as gliomas, squamous carcinomas, and breast cancers, is presented. EGF and sulfhydryl boron hydride (BSH) were covalently coupled to an allylated 70 kDa dextran chain to form a conjugate. Conjugates with low and high substitution rates of BSH, as well as without BSH, were investigated. The conjugate with a low amount of boron had approximately 6 BSH (72 boron atoms) per dextran, while the conjugates with higher amounts had an average substitution of 55 BSH (660 boron atoms) per dextran. The maximum substitution of boron to dextran in a single experiment was over 800 boron atoms. Binding, retention, and internalization of 125I-labeled conjugates were investigated on cultured human glioma cells. Binding of the conjugates was EGF receptor specific, but the amount of BSH coupled to dextran affected specificity, more than the presence of dextran. The nonspecific binding of the conjugates increased with the amount of attached boron. This was partly due to nonspecific adhesion to the plastic in the culture dishes. [125I]EGF-allyldextran with 6 BSH had a binding maximum after 4 h of continuous incubation and thereafter decreased in binding, while [125I]EGF-allyldextran with the higher substitution rate had a slow increase of binding during 24 h. Over 93% of the radioactivity bound to the cells was internalized, but the retention was quite poor. Only one-third of the cell-bound activity was still associated to the cells 4 h after incubation had ended. In conclusion, it is possible to load the conjugates produced with high amounts of boron, and they retained specificity for the EGF receptor and internalized into cultured cells. Theoretical calculations show that about 10(3) boron atoms per EGF-based conjugate are needed to give a satisfactory therapeutic response. These conjugates are within reach of that level.

Boron Neutron Capture Therapy↗

Dose monitoring for boron neutron capture therapy using a reactor-based epithermal neutron beam.

The aims of this study were (i) to determine the variation with time of the relevant beam parameters of a clinical reactor-based epithermal neutron beam for boron neutron capture therapy (BNCT) and (ii) to test a monitoring system for its applicability to monitor the dose delivered to the dose specification point in a patient treated with BNCT. For this purpose two fission chambers covered with Cd and two GM counters were positioned in the beam-shaping collimator assembly of the epithermal neutron beam. The monitor count rates were compared with in-phanton reference measurements of the thermal neutron fluence rate, the gamma-ray dose rate and the fast neutron dose rate, at a constant reactor power, over a period of 2 years. Differences in beam output, defined as the thermal neutron fluence rate at 2 cm depth in a phantom, of up to 15% were observed between various reactor cycles. A decrease in beam output of about 5% was observed in each reactor cycle. An unacceptable decrease of 50% in beam output due to malfunctioning of the beam filter assembly was detected. For safe and accurate treatment of patients, on-line monitoring of the beam is essential. Using the calibrated monitor system, the standard uncertainty in the total dose at depth due to variations with time of the beam output parameters has been reduced to a clinically acceptable value of 1% (one standard deviation).

Boron Neutron Capture Therapy↗

A review of techniques for the analysis of boron in the development of neutron capture therapy agents.

The resurgence of interest in neutron capture therapy, which uses boron-10 labelled compounds and neutron irradiation as a technique for the treatment of cancer, has been accompanied by the application of a new generation of techniques for the analysis and imaging of boron in biological matrices. In this review, a description is given of the requirements for boron neutron capture agents and the achievements to date of the analytical techniques.

Animals↗

Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the epithermal neutron beam at the Brookhaven National Laboratory.

OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. RESULTS: 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Aged↗

Electron microscopic study on the response of the normal canine brain to boron-neutron capture therapy.

The response of normal cerebral tissue of dogs to boron-neutron capture therapy by the currently available improved method was studied by electron microscopy. Peripheral blood capillaries of the neutron-irradiated area in the left cerebral hemisphere were compared with their counterparts in the shielded and non-irradiated right hemisphere. No ultrastructural changes, as those noted in classical method of boron-neutron irradiation by the improved technique of boron-neutron capture therapy. There was no swelling of endothelial cells, disappearance of cristae of mitochondria, increased pinocytosis, disappearance of ribosomes, enlargement of Golgi apparatus, or increased appearance of endoplasmic reticulum. Basement membrane was not disrupted and was uniform. Pericytes, synaptosomes, and other glial elements remained intact. In contrast to the old clinical trials up to 1961, the renewed boron-neutron capture therapy is regarded not to cause serious damage to the central nervous system.

Animals↗