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• BNCT, what is it?
• BNCT, facility (photo 120 kb)
• Other location for clinical trials
 
 

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BNCT what is it? A possible treatment of brain tumors.

NRG (in the past: ECN) uses the knowledge of radio active materials and radiation for the development of a special type of radiotherapy, which is suitable for the treatment of brain tumors. this therapy, the Boron Neutron Capture Therapy (BNCT) is based on two phenomena:
  1. the preferential uptake by the tumor of certain boron compounds, and
  2. the fission of the borium nucleus after absorption of a neutron for instance a neutron from the High Flux Reactor or the Low Flux Reactor in Petten. The particles emitted (helium-nuclei) with this nuclear reaction and lithium particles destroy the tumor cells.

NRG manages clinical facilities that (image: 120k) have been installed near the High Flux Flux Reactor of the JRC in Petten. There are plans to use the Low Flux Reactor for BNCT too.

BNCT: the demonstration phase has started!

After some years of preperations the first patient with a brain tumor was treated using BNCT in 1998. During a number of years there will be a period of clinical trials. Patients will be treated with different doses and different intervals and examined by medical doctors to evaluate the toxicity and effectivity of the treatment. After these so-called phase I/II clinical trials, patient treatments in Petten may become a more standard procedure.
Mid 1999 the results of the first trial period were evaluated and they were encouraging.

BNCT: an international project

The BNCT-project is a European project in which many European countries participate. In the Netherlands the major share of the work is performed by:
  • het Nederlands Kanker Instituut,
  • GCO-Petten en
  • NRG.

NRG contributes its nuclear and radiobiological expertise, collected during 40 years of research.

In Japan and the United States progress on BNCT is reported too. In Brookhaven (US) the first BNCT treatment was conducted in 1994, using the Brookhaven Medical Research Reactor. The apparent successes of these early treatments increases our.
The facility in Petten has some advantage on other facilities because it has a almost parallel bundle which makes it easier for our staff in Petten to bring the patient into the right position and to administer the required dose.

BNCT: Old idea, new technique

BNCT is not a new idea. Already in 1936, just four years after the discovery of the neutron, the nuclear reaction of boron with a neutron into lithium with an alpha particle (10iB(n,)7Li) was seen as a way to treat tumors. A boron atom that absorps a neutron ejects an -particle (helium nucleus) and changes into a lithium atom. The two reaction products have enough energy to damage a cell permanently. Such particles will travel only a very short distance in biological material, usually just a few micrometers. The typical diameter of a cell, so also of a cancer cell, is 10 micrometer. The particles therefore will only damage cells that selectively accumulated boron.

So what one has to do is to bring boron into the tumor to be able to destroy the tumor with a neutron beam. The integration of these two steps into a therapeutical treatment offers a considerable challenge. Medical doctors, chemists and pharmacists have to make a compound containing boron and that has the property to accumulate in cancer cells and not in healthy cells.
The physicists have to make the appropriate neutron beam : a beam of neutrons that has to arrive at a certain depth in the body with the right speed. The reaction with boron is best with thermal (slow) neutrons.

In the 1950s the first clinical trails were undertaken. The results were not very encouraging and the trials were stopped. The compound that carried the boron was not selective enough and unacceptable damage occured in healthy brain tissue. Meanwhile science and technology have advanced considerably and application of the 'old' BNCT idea offers much better prospects.

Mathematical models for Microdosimetry

During the irradiation the reaction rate can be monitored because with the nuclear reaction gamma radiation is also emitted. The minute radiation can be measured. With this information the amount of energy absorbed in the tumor can be calculated.

For the translation of these measurements to the damage to the cancer cell a dose effect relation has to be established. Existing models are not adequate. therefore NRG developed its own model for microdosimetry. This model gives a prediction of the therapeutic affect of a complete BNCT treatment. It calculates the energy dissipated in the cells.

BNCT: clinical trials

In four European hospitals pharmaceutical research has been conducted into the accumulation of boron by the tumor an boron concentration versus time. Patients that were waiting for a operation were administered boron, after removal of the tumor the boron concentration in the tumor was measured.

In the radio-biological part of the BNCT-project a study with dogs was undertaken. The radiation tolerance of brain cell was evaluated and the biological dosimetry was developed. By irradiation of several dogs a good dose-effect relationship has been established, which enabled the start of clinical trials with humans. The experiment was needed to find the maximal permittable dose level for healthy brain tissue.

Sensitivity brain cells

From the research into the sensitivity of stem cells in the brain it can be concluded that the cells are more sensitive to fast neutrons than originally anticipated. In the HFR cylinder filled with water was irradiated. In the cylinder at several positions stem cells were present with known boron concentrations. Whith this facility - called a phantom - a human being is modelled. this is possible since the human body consists for the major part of water.
After monitoring the irradiated cells the percentage that survived was established and in this way the neutron flux distribution over the phantom body. The results showed good agreement with results with other techniques used by physicists to measure fluxes and flux distributions.
The results of the flux calculations with the Monte Carlo Neutron and Photon Transport Code, initially were not satisfactory. After incorporating in the model the neutron scattering in water this problem was solved.

BNCT and the Low Flux Reactor

In Petten there is a second reactor. Near the High Flux Reactor of JRC-Petten, operated by NRG staff, there is a second smaller reactor. The Low Flux Reactor (LFR) of NRG/ECN is a facility for irradiation with thermal neutrons that is used for experiments with cells and small animals. These experiments have yielded satisfactory results and thus it is clear that the LFR offers the possibility of clinical applications of thermal neutrons, especially for the treatment of tumors on the surface of the body.

Petten can become a unique center where several types of tumors can be treated, whether they may be on the surface of the body or deeper in the body.
 
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Update 5 March 2002