Neutron Capture Therapy

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Neutron Capture Therapy (NCT) by means of Compact Neutron Generators (CNG)

The recent techniques of protein synthesis, the progress of biological knowledge on the structure of neoplastic cells and the improvement of microdosimetry methods have provided a remarkable contribution to the development of the Neutron Capture Therapy, a form of therapy for the treatment of some types of tumours which present an unsatisfactory answer to usual medical treatments (traditional radiotherapy and chemiotherapy).

The Neutron Capture Therapy (NCT) was applied:

  1. at the beginning of the fifties in USA and in Japan, for the treatment of brain Glioma (and partially of melanomas);
  2. at the beginning of the nineties in Sweden, Holland, Finland, Czech Republic for the treatment of brain Glioma;
  3. recently, for the treatment of liver tumours with the technique of the autotransplantation nearby the University of Pavia.

While early studies of the fifties did not emphasize substantial advantages compared to other treatments, more recently the NCT allows to obtain:

  1. An improvement of life quality for the patient
  2. A general extension of the life expectation of the treated patients
  3. The complete healing (above all for the liver tumour with the technique of the autotransplantation).

The advantage of the NCT compared to the traditional radiotherapy consists in the use of radiations with high LET (Linear Energy Transfer, generally expressed in keV/µm). The use of high LET radiations in the treatment of tumours is based on an elementary consideration: for the same absorbed dose, high LET radiations produce a higher damage to the target cells.

Anyway, the problem of the cure of neoplasias is not reduced only to considerations about a bigger or smaller damage in absolute value to the tumoral cells because differential evaluations of damages caused to tumoral cells in comparison with those caused to healthy tissues are definitely necessary.

Therefore, the precision level with whom the neoplastic part is identified, results essential to achieve positive differential effects.

To that end, the mentioned development of techniques of protein synthesis, made possible the production of substances able to concentrate themselves with good selectivity on the tumoral cells compared to the healthy cells.

Today the further biochemical progress about the possibility to combine other atoms or molecules with these proteins permits to have good vectors able to carry different substances on the tumoural cells.

These techniques allow to carry on the neoplastic formations both damaging substances and elements that are able to define boundary and size.

In particular, substances able to carry and fix atoms of the isotope Boron-10 on some types of tumours have been synthesized.

Later, irradiating with neutrons of proper energy tissues enriched with this isotope, a nuclear reaction (n, α) is induced and breaks the nucleus of Boron-10 in two highly energetic fragments. To this reaction is associated a considerable radiation dose at high LET and short range, that is able to produce remarkable damages only to the cells in proximity of the Boron-10 atom hit by the neutron.

This is, in short, the principle on which is based the NCT and, in particular, the so-called Borotheraphy or Boron Capture Theraphy (BNCT). This is a typical form of binary theraphy because it is characterized by two separate but combined and indispensable phases to irradiate tumoral tissues with necessary doses:

  1. Concentration of atoms which absorb neutrons (especially Boron-10 and Gadolinium), in a selective way into the neoplastic cells.
  2. Irradiation of the tumoral area with beams of thermic and/or epidermic neutrons, with consequent nuclear reactions and induction of localized damage to the neoplastic cells.

The therapeutic application of the NCT is connected to the availability of high neutron fluxes able to reach tumoral cells. At the moment this condition has only been realized by means of nuclear reactors but, with the development of devices as the Compact Neutron Generators described in the previous chapter, the therapeutic application of the NCT will be possible in the radiotherapy units of the Hospitals and Institutes involved in research and treatment of tumours.

The CNG is the most promising neutron source for all the systems designed for the application of NCT in Hospitals. In addition to CNG these systems include the presence of suitable/appropriate materials that for their physical, nuclear and geometric characteristics collect neutrons emitted isotropically from CNG (reflecting materials), address them towards the patient’s area treatment (exit window of the neutron beam) and reduce the energy until best value to maximise the effectiveness of the treatment (moderator materials).

In the picture 1 it is showed a simplified scheme of a system for the hospital application of NCT based on a neutron source of NCT type.

 

Picture 1 simplified scheme of a system for the hospital application of NCT

The moderator and reflector allow to slow down neutrons and limit leakage optimazing their energy in order to irradiate the tumoral mass successfully.

The picture 2 shows a three-dimensional image of a system for the application of Borotheraphy in hospitals, that supplied of right shields and safety systems could be installed in a normal unit of radiotheraphy and/or nuclear medicine.

The theraphy area where the patient is located, gives an idea of the global dimensions of the device made up of a neutron source, shields and auxiliary systems.

 

Picture 2 integrated systems for the therapeutic application of NCT (artistic view)

According to the type of neoplasias that have to be treated it is possible to study different optimizations of the device, including the opportunity of modifying only a limited part of it. The reduced dimensions allow the modularity and, so, the possibility to treat different neoplasias changing only some parts of the device. For example, modifying only the terminal part of the device is possible to get more or less energetic neutrons.

In the case of superficial tumours (melanomas or liver neoplasias with the technique of the autotransplantation) is advisable a little energetic neutron fluxes, or rather mainly thermal, while in the case of deep tumours (typically brain tumours) is better a more energetic neutron fluxes (epithermic or also directly fast neutrons) because, on the contrary, neutrons will not be able to reach the tumoral mass.

The CNG, integrated with all the auxiliary systems previously listed, can be located inside a radiotheraphy unit or a nuclear medicine laboratory.

To that end, it is necessary to include the availability of:

  • A normal electric three-phase power supply
  • A limited flow of demineralized water
  • A ventilation system of the therapy room
  • Neutron shields (for instance in concrete or borate water) for the device and the therapy area.
  • An access system to the therapy room regulated by interblocks

The picture 3 shows an example of lay-out of a radiotherapy unit or a nuclear medicine laboratory involved in the application of NCT through an integrated system based on the use of GNG.