Four groups of 10 patients, suffering from a particularly malignant
cervical tumour, have embarked on a new form of radiotherapy. This
first clinical trial, based on boron neutron capture therapy (BNCT),
is the result of 10 years of collaboration between the leading specialists
in Europe. This advance in radiotherapy has been made possible thanks
to the equipment and knowhow of the Joint Research Centre (JRC), Petten.
High-flux reactor (HFR) of the JRC Institute
for Advanced Materials.
Every year, throughout the world, more than
six million treatments, diagnoses and therapies are carried out in
departments of nuclear medicine with the help of "European" radioisotopes.
This "raw material" for nuclear medicine is produced by the High Flux
Reactor (HFR) of the Institute for Advanced Materials (IAM) of the
Joint Research Centre (JRC) in Petten (Netherlands). Originally intended
solely for research in nuclear fusion and fission, the HFR has now
discovered a second vocation.
From fusion to nuclear medicine
While it is true that the discovery of boron neutron capture dates
back more than half a century, its application in the field of medicine
is characterised by decades of trial and error. As long ago as 1936,
only four years after the American biophysicist J. Chadwick discovered
neutrons, G.L. Locher proposed that one of the special features of
neutrons be used in the therapeutic domain. Subjecting boron atoms
to low-energy neutron radiation (thermal neutrons) causes the boron
nuclei to disintegrate into alpha particles and lithium isotopes with
a kinetic energy of 2.5 MeV. When this disintegration occurs in the
malignant cells, the energy generated is sufficient to destroy them
without damaging the neighbouring cells, since the range of the particles
is only 10 microns.
The HFR is a 45 MW reactor intended initially for conducting experiments
on nuclear materials and fuels in the context of European civil
programmes. Over the last few years, its scope has been extended
to include medicine, and in particular the production of radioisotopes
and boron neutron capture therapy, which is a very specialised form
of radiotherapy. More than a third of its capacity is used for the
production of radioisotopes employed mainly in the treatment of
cancers, and it is now the principal supplier of such isotopes in
At the heart of the cells
"From a clinical point of view, however, BNCT only becomes an attractive
proposition if a sufficient dose of thermal neutrons reaches the
target cells and if the concentration of boron is high in the tumour
and low in the surrounding healthy tissue," explains Raymond Moss,
the scientist responsible for the BNCT programme at the HFR. These
two constraints help to explain the long years of preparation and
the failures associated with the initial tests of BNCT in the United
"Since the early 1980s, there has been a better understanding of
the biology of boron neutron capture therapy, and major progress
has been made in the field of boron compounds and neutron beams,"
adds Wolfgang Sauerwein of the University of Essen (Germany), the
clinician responsible for treating patients at Petten. "Before the
first irradiations carried out with the help of the HFR, numerous
pharmaco-kinetic tests had been conducted over the previous 10 years
- with the support of the BIOMED I programme - by the research centres
associated with this experiment." These tests made it possible to
select a boron-sodium compound found in the cancerous cells of cerebral
tumours, but not in the cells of a healthy brain. In parallel, the
HFR researchers developed a process for the production of neutron
beams of sufficiently high energy to reach deep-seated cells.
This double-edged European research work has enabled us to take
a step forward in our approach to cancer treatment. BNCT is currently
being tested on cases of glioblastoma multiforme, a brain tumour
that recurs persistently, shows little response to conventional
treatments and affects 15 000 Europeans each year.
Inauguration of the radiotherapy centre
at the Joint Research Centre (JRC), Petten.
First clinical trials
This European project entered phase I clinical trials in October
1997. Four groups of 10 patients from five countries (Germany, Netherlands,
France, Switzerland and Austria) were selected for these trials
which are being conducted under the control of the NDDO (New Drug
Development Office) of the EORTC (European Organisation for Research
and Treatment of Cancer) and to be funded under the Biomed II programme.
Between two and six weeks after surgery in their country of origin,
the patients - for whom existing known treatments offer no further
hope - are transferred to the Free University of Amsterdam Hospital.
For a period of four days they are taken to the HFR for daily treatment
lasting 20 minutes and carried out by specialists from the University
of Essen. They then return to their own country for intensive monitoring.
"The aim of the present study is to assess the toxicity of the
treatment and to establish the tolerance of the healthy tissue,"
explains Wolfgang Sauerwein. "If we were to find evidence of a therapeutic
effect, that would of course be marvellous, but concentration on
anti-cancerous activity proper is not due to commence until the
next stage, i.e. the phase II tests."
JRC Research : Institute for Advanced Materials