Paolo,

I read a brain tumor news letter last week reporting that a patient had
survived GBM (astrocytoma grade IV) for 12 years!  This patient initially
went through many surgeries and chemo treatments but finally obtained a
period of remission that has persisted for over 6 years.  Typical GBM
patient survives less than 1 year so there is always hope albeit remote.

Best wishes to your friend,
Bill

Well I'm confused. Did they not get it all out?

Maybe Steph would explain how it would be treated in Canada.
J

The treatment sounds promising. Remember it is experimental therefore
unproven. It will interesting to see what the doctors say after the new
treatment, best of luck, Alex

http://www.ieo.it/inglese/scicontrib/radioimm.htm
Radioimmunotherapy with Avidin-Biotin
The new therapeutic strategy, named 3-step-pretargeting, consists of tumour
targeting through monoclonal antibodies and of tumour destruction the through a
radioactive isotope guided to the antibody via the avidin-biotin system.

Conventional Radioimmunotherapy
Until a few years ago, radioimmunotherapy was based on the direct administration
of radioactive monoclonal antibodies. Monoclonal antibodies, extraordinary tools
developed with the hybridoma technique by genetic engineers, have the same
properties as natural antibodies produced by the immune system: they recognise
specific proteins (called antigens) present on the tumour. These monoclonal
antibodies, capable of recognising specific tumoral antigens, have been used by
conventional radioimmunotherapy to transport a radioactive agent capable of
destroying the tumoral cell.
The limitation of the technique is that only a small percentage of the labelled
antibody binds to the tumour (about 1%), while the majority of the antibodies
continue to circulate in the blood stream and diffuse to different parts of the
organism, accumulating radioactivity in healthy tissues particularly in the
kidneys, liver, and bone marrow, which may cause damage.
The New Technique With Avidin-Biotin
The step forward, made at the European Institute of Oncology, consists in the
development and implementation of a system able to prevent the diffusion of the
radioactive antibodies. Like conventional radioimmunotherapy, pretargeting is
based on the use of monoclonal antibodies. In this case, however, the antibodies
are rendered radioactive only after they have reached their destination and only
after those dispersed have been eliminated. In fact, after administration,
monoclonal antibodies bind to the tumour in around 24-48 hours and remain there
for another 3-5 days, while the fraction dispersd in the organism is eliminated
through the urine in 2-3 days.

In order to deliver the radioactive agent to the tumour, Dr. Paganelli has
designed a system that takes advantage of the natural attraction that exists
between two molecules: avidin and biotin. Avidin is a protein present in the egg
white, which is able to form a very stable bond with four molecules of biotin,
which is a vitamin (vitamin H).

3-Step-Pretargeting With Avidin-Biotin
The therapeutic plan of this new radioimmunotherapic technique is performed in
three phases:

First Step
On the first day, the patient receives an endovenous injection of monoclonal
antibodies previously bound to biotin molecules.
These antibodies will reach their target (the tumour) in 24 to 48 hours.

Second Step
24-48 hours after the first injection, the patient receives another endovenous
injection, this time of avidin. Due to the high affinity between these two
molecules, avidin will bind to the biotin, which is already present on the
tumour. The avidin molecules that remain in circulation will be metabolised by
the liver. Each molecule of avidin has 4 small pockets where molecules of biotin
can be bound.

Third Step
On the third day, when dispersed antibodies have been eliminated, the patient
receives the last injection: a dose of biotin, which has been previously
labelled with a radioactive isotope. In this way, the radioactive biotin is
strongly attracted by the avidin present on the tumour and reaches its specific
target in few minutes, destroying it. Radioactive biotin not bound to the tumour
is rapidly excreted through the kidneys since it is a very small molecules.

The Risult
Presently, this type of immunoradiotherapy has been applied only in advanced
stage tumours, in which other therapies have failed. The types of tumour that
seem more sensitive to this type of therapy are those of the brain, the ovary,
and lymphomas. Although the treatment is tolerated well and is free of the
undesirable side effects of other conventional therapies, it is necessary to
highlight that it is still an experimental therapy, indicated only for certain
types of neoplasms, and only when the tumour is smaller than 2-3 centimetres in
diameter.

The pretargeting system with avidin-biotin represents a promising model of
radioimmunotherapy. In theory, it can be applied to all types of tumour for
which specific antibodies are available. Although complex, the system is not
difficult to apply. It requires, however, a specially equipped area for the
manipulation of radioisotopes.
Essential References

Cancer Res /Vol 51: 5960-6, 1991

J Nucl Med /Vol 33:1110-2, 1992

J Nucl Med /Vol 37:967-71, 1996

European Journal of Nuclear Medicine /Vol 24: 350-1, 1997

European Journal of Nuclear Medicine / Vol 25: 1336-9, 1998

European Journal of Nuclear Medicine /Vol 26:348-357, 1999

 Last revised: August 2002 <end quote>

Steph comment?
J

How's it going Paulo?
(I see Steph hasn't noticed or commented on the therapy, so I'm posting it
separately.
Keep in touch,
J