Language and medicine in the Zamenhof family.

The Zamenhof family is famous for Dr Ludwik Lejzer Zamenhof (1859-1917), who created the artificial language Esperanto and who initiated a social movement for peace and against any sort of discrimination. Ludwik was an ophthalmologist. Adam, Leon, Alexander, and Julian Zamenhof were medical doctors and noted surgeons, while Sophia Zamenhof was a paediatrician.

Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT).

Boron Neutron Capture Therapy (BNCT) is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having a high biological effectiveness and a very short range in tissue, being limited to approximately one cell diameter. This opens the possibility for a highly selective cancer therapy. BNCT strongly depends on the selective uptake of 10B in tumor cells and on its distribution inside the cells.

Voxel model in BNCT treatment planning: performance analysis and improvements.

In recent years, many efforts have been made to study the performance of treatment planning systems in deriving an accurate dosimetry of the complex radiation fields involved in boron neutron capture therapy (BNCT). The computational model of the patient's anatomy is one of the main factors involved in this subject. This work presents a detailed analysis of the performance of the 1 cm based voxel reconstruction approach.

Calculated DNA damage from gadolinium Auger electrons and relation to dose distributions in a head phantom.

Purpose: To calculate the number of 157Gadolinium (157Gd) neutron capture induced DNA double strand breaks (DSB) in tumor cells resulting from epithermal neutron irradiation of a human head when the peak tissue dose is 10 Gy. To assess the lethality of these Gd induced DSB. MATRIALS AND METHODS: DNA single and double strand breaks from Auger electrons emitted during 157Gd(n,gamma) events were calculated using an atomistic model of B-DNA with higher-order structure.

The microdosimetry of the (10)B reaction in boron neutron capture therapy: a new generalized theory.

The microdosimetry of (10)B thermal neutron capture reactions should be considered as an essential step to be followed before studying the radiobiological aspects of boron neutron capture therapy. The boron dose itself is insufficient as the only quantity used to describe the biological effectiveness of the (10)B reaction for two important reasons: the specific microdistribution that the (10)B carrier compound exhibits at the cellular level and the primarily stochastic nature of the energy deposition process, which influences the biological response to the particulate radiation. In this work, these two aspects are analyzed in detail and an innovative rigorous analytical framework is developed in the microdosimetry domain.

Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam.

A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.

Dose-rate scaling factor estimation of THOR BNCT test beam.

In 1998, an epithermal neutron test beam was designed and constructed at the Tsing Hua Open-Pool Reactor (THOR) for the purpose of preliminary dosimetric experiments in boron neutron capture therapy (BNCT). A new epithermal neutron beam was designed at this facility, and is currently under construction, with clinical trials targeted in late 2004. Depth dose-rate distributions for the THOR BNCT test beam have been measured by means of activation foil and dual ion chamber techniques.

Moderated 252Cf neutron energy spectra in brain tissue and calculated boron neutron capture dose.

While there is significant clinical experience using both low- and high-dose (252)Cf brachytherapy, combination therapy using (10)B for neutron capture therapy-enhanced (252)Cf brachytherapy has not been performed. Monte Carlo calculations were performed in a brain phantom (ICRU 44 brain tissue) to evaluate the dose enhancement predicted for a range of (10)B concentrations over a range of distances from a clinical (252)Cf source. These results were compared to experimental measurements and calculations published in the literature.

Pharamacokinetic modeling for boronophenylalanine-fructose mediated neutron capture therapy: 10B concentration predictions and dosimetric consequences.

A two-compartment open model has been developed for predicting 10B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The 10B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32 +/- 0.

A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease.

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory.

A theoretical model for the microdosimetry of discontinuous distributions of heavy particle tracks.

A novel approach to solving microdosimetry problems using conditional probabilities and geometric concepts has been developed. This approach is valid for cases where a convex site is immersed in uniform or discontinuous distributions of heavy charged particle tracks and assumes no restrictions in site geometry or the kind of randomness. These conditions are relevant to the study of microdosimetry in applications such as neutron capture therapy (NCT), irradiation experiments using heavy ion particle beams, environmental radon, or occupational exposure to radioactive materials.

Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy.

Purpose: A Phase I trial of cranial neutron capture therapy (NCT) was conducted at Harvard-MIT. The trial was designed to determine maximum tolerated NCT radiation dose to normal brain.

Methods And Materials: Twenty-two patients with brain tumors were treated by infusion of boronophenylalanine-fructose (BPA-f) followed by exposure to epithermal neutrons.

Reference dosimetry calculations for neutron capture therapy with comparison of analytical and voxel models.

As clinical trials of Neutron Capture Therapy (NCT) are initiated in the U.S. and other countries, new treatment planning codes are being developed to calculate detailed dose distributions in patient-specific models.

A theoretical model for event statistics in microdosimetry. II: Nonuniform distribution of heavy ion tracks.

A microdosimetry model, described in Part I, applies to the case of a convex site immersed in a uniform distribution of heavy particle tracks, and assumes no restrictions in site geometry or the kind of randomness. In Part II, this model is extended to include nonuniform distributions of particle tracks. This situation is relevant to the study of microdosimetry, for example, in boron neutron capture, in irradiation experiments using heavy ion particle beams, where the sources of particle tracks are external to the cell, or in irradiation from internally incorporated particle-emitting radionuclides, such as environmental radon or occupational exposure to radioactive materials.

A theoretical model for event statistics in microdosimetry. I: Uniform distribution of heavy ion tracks.

In this work we describe a novel approach to solving microdosimetry problems using conditional probabilities and geometric concepts. The intersection of a convex site with a field of randomly oriented straight track segments is formulated in terms of the relative overlap between the chord associated with the action line of the track and the track itself. This results in a general formulation that predicts the contribution of crossers, stoppers, starters, and insiders in terms of two separate functions: the chord length distribution (characteristic of the site geometry and the type of randomness) and an independent set of conditional probabilities.

A pharmacokinetic model for the concentration of 10B in blood after boronophenylalanine-fructose administration in humans.

An open two-compartment model has been developed for predicting (10)B concentrations in blood after intravenous infusion of the l-p-boronophenylalanine-fructose complex (BPA-F) in humans and derived from studies of pharmacokinetics in 24 patients in the Harvard-MIT Phase I clinical trials of BNCT. The (10)B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biphasic exponential clearance profile with half-lives of 0.34 +/- 0.

Computational validation of the stereology principle applied to the microdosimetry of boron neutron capture therapy.

High resolution quantitative autoradiography (HRQAR) is a novel technique that has been developed in our laboratory and applied to the microdosimetry of boron neutron capture therapy (BNCT). High resolution quantitative autoradiography is employed to define the microdistribution of boron-10 atoms within a 1-2 microm frozen tissue section. This microdistribution is used as input to a novel two-dimensional Monte Carlo charged particle transport calculation that computes various microdosimetric parameters, such as the number of nuclear "hits," energy absorbed in the nuclei, etc.

Proton nuclear magnetic resonance measurement of p-boronophenylalanine (BPA): a therapeutic agent for boron neutron capture therapy.

Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.

Microdosimetry for boron neutron capture therapy: a review.

A review of the microdosimetry of boron neutron capture therapy is presented focusing on the progression of key scientific ideas and developments in this field rather than on a comprehensive and inclusive review of the literature. The author concludes that from a microdosimetry perspective the field is highly advanced, but what is lacking is the correlation of the proposed models and results with experimental radiobiological data.

Monte Carlo-based treatment planning for boron neutron capture therapy using custom designed models automatically generated from CT data.

Purpose: A Monte Carlo-based treatment planning code for boron neutron capture therapy (BNCT), called NCTPLAN, has been developed in support of the New England Medical Center-Massachusetts Institute of Technology program in BNCT. This code has been used to plan BNCT irradiations in an ongoing peripheral melanoma BNCT protocol. The concept and design of the code is described and illustrative applications are presented.

A novel approach to the microdosimetry of neutron capture therapy. Part I. High-resolution quantitative autoradiography applied to microdosimetry in neutron capture therapy.

A novel approach to the microdosimetry of neutron capture therapy has been developed using high-resolution quantitative autoradiography (HRQAR) and two-dimensional Monte Carlo simulation. This approach has been applied using actual cell morphology (nuclear and cytoplasmic cell structures) and the measured microdistribution of boron-10 in a transplanted murine brain tumor (GL261) containing p-boronophenylalanine (BPA) as the boron compound. The 2D Monte Carlo transport code for the alpha and 7Li charged particles from the 10B(n,alpha)7Li reactions has been developed as a surrogate to a full 3D approach to calculate a variety of different microdosimetric parameters.

Spurious dual-energy X-ray absorptiometry images in a patient exposed to the contrast agent Thorotrast.

A 69-year-old woman presented with a 20-year history of back pain and a 10 cm height loss. She had received an injection of the contrast agent, Thorotrast, at age 23. There was no history of fluoride exposure.

Boron neutron capture therapy for murine malignant gliomas.

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival.