01.12.2020 change 03.12.2020

Microspheres from the Świerk's MARIA reactor help patients with liver cancer

Photo: press materials Photo: press materials

The MARIA research reactor is one of the main irradiation centres for microspheres containing radioactive holmium, used in the treatment of liver tumours. The technology developed at NCBJ helps patients in several specialized centres in Europe.

Head of Reactor Research at the National Centre for Nuclear Research, Dr. Rafał Prokopowicz, said that microspheres with a diameter of about 30 micrometers made of holmium polylactide (a polymer of lactic acid) are used for local radiotherapy, mainly in the case of liver tumours. At the production stage, stable isotope holmium-165 is placed in them, which can then be transformed into the radioactive holmium-166 isotope by neutron bombardment.

Holmium-166 has a number of useful properties; its life is relatively short (approx. 27 hours), and when decaying it emits beta radiation with an energy of approx. 2 MeV, which has a tissue penetration range of several millimetres.

Trapped in microspheres, radioactive holmium is administered mainly to patients with advanced liver tumours by injecting the suspension with the microspheres into the appropriate blood vessels leading them to the tumour site. Acting locally, beta radiation destroys cancer cells, leaving most of the healthy part of the organ intact. This procedure is called radioembiolization. It is used in the case of inoperable tumours not susceptible to chemotherapy. Holmium has two additional advantages: it also emits gamma radiation, which can precisely locate the radioactive substance injection site and determine its dose. It is also paramagnetic, which creates additional possibilities, e.g. for tracking the administered substance in the body.

The only holmium-containing microspheres currently used in therapy are produced and distributed by the Dutch company Quirem Medical B.V. as QuiremSpheres. In 2017, in cooperation with Quirem Medical, a team of scientists working at the MARIA reactor started to develop a technology for irradiating holmium microspheres. 

Dr. Prokopowicz said: “The task required the adaptation of the reactor infrastructure and the development of new technological solutions, procedures and a new methodology for irradiating target materials.

“The reason for this is that each vial of microspheres contains an aliquot prepared for the treatment of a specific patient and should be irradiated in such a way that it has the appropriate activity specified for that patient at the designated date and time of treatment.”

Every material is heated during the irradiation process. Polylactide microspheres are very sensitive to temperature: their degradation can start after reaching 60° C. However, they must retain their shape during irradiation so that they can easily reach the treated area after being administered to the patient.

Prokopowicz added: “To improve the irradiation conditions of microspheres, we have improved the cooling system for the containers with microspheres placed in the reactor. It was also necessary to place special radiation detectors in the reactor core, right next to the irradiation site, to monitor the conditions. 

“We created a special algorithm and a computer program based on it. It analyses signals from detectors and facilitates a very precise determination of the irradiation time of individual containers with microspheres, so that they obtain the activity required during the therapy. It is a key tool for the correct irradiation of microspheres, as the neutron flux density in the reactor changes during its operation.”

NCBJ scientists in cooperation with Quirem have also developed special vials for irradiating microspheres, named the MARIA vials after the name of the reactor. The secret of these vials is the specially profiled bottom, which causes the material placed in the container to form a thin, relatively well-cooled layer. 

The technology was developed at NCBJ on behalf of Quirem Medical. Vials with microspheres for the needs of over 100 patients per year are currently irradiated in the MARIA reactor. They are used in many clinics all over Europe, incl. centres in Rotterdam, Nijmegen, Utrecht, Dresden, Magdeburg, Jena, Basel, Rome, Pisa, Barcelona, Madrid, Porto and others. For over three years, the MARIA reactor has been one of the few and at the same time main sites for irradiating microspheres for Quirem. 

Since the needs for the implementation of therapy appear shortly in advance, the reactor team must be ready almost 24/7 to prepare and conduct irradiation and dispatch microspheres. This requires the involvement and constant readiness of many specialists.

Dr. Michał Gryziński, director of the NCBJ Nuclear Facilities Operation Department, said: “We hope to build a laboratory at the MARIA reactor, which will allow NCBJ to become a distribution centre for QuiremSpheres microspheres in Eastern Europe and Poland, where this form of therapy is not yet available.”

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