CERN Accelerating science

The CERN-MEDICIS project

by Panos Charitos

Secondary radioactive ion beams have been delivered to ISOLDE at CERN for over 40 years, for fundamental studies in nuclear structure and for applications, for instance in semi-conductors. The idea of using these beams as sources for innovative medical isotopes was put forward fifteen years ago by G. Beyer and collaborators. However both beam time access and proper infrastructures to handle open radioactive sources suitable for these applications were lacking. Recently, the initiave to develop suitable infrastructures received support from external medical and cancer research partners, from the KT-Fund selection board, from CERN directorate, and has now become the CERN-MEDICIS project.

CERN MEDICIS is a research facility that will make radioisotopes for medical applications. Earlier in September the construction of the new MEDICIS facility began and it will start operating in 2015-2016. The new facility will offer more time for investigation of new isotopes as well as it will allow exploring different novel techniques for medical applications. As Thierry Stora, the CERN engineer who leads the CERN MEDICIS project says: “By building this new infrastructure, the MEDICIS collaboration, can actually reach a level that was never possible before”.

To produce radioisotopes CERN MEDICIS will use the primary proton beam at ISOLDE.  At the ISOLDE facility, physicists bombard various targets with beams of protons. At ISOLDE, a high-energy, high-intensity proton beam from the Proton-Synchrotron Booster hits a target where the beam loses only 10% of its intensity and energy on hitting the target –degrading from 1.4 GeV to 1.3 GeV- so the particles that pass through can still be used.

The beams of protons from the PS Booster will lose only 10% of their energy by interacting with the ISOLDE target. By slightly modifying the geometry a second target can be installed for researching new isotopes with MEDICIS. In this way many targets can be used without affecting the beam that is delivered to ISOLDE; in that sense MEDICIS will be transparent for ISOLDE (Image:CERN).

 

Adding a second target for MEDICIS behind the first will allow a significant portion of the beam to be re-used for creating new "medical" isotopes. The isotopes will be produced in targets just before the HRS beam dump position while recycling the unused PSB proton beam. In that sense MEDICIS is transparent to the operation of ISOLDE and the accessibility to a variety of isotopes will almost double.

In 2012, test collection of a small batch of 152Tb was done at ISOLDE by the MEDICIS collaboration and shipped to Lausanne university hospital, CHUV. Biodistribution studies of a new bombesin analogue bioconjugate showed better retention in prostate cancer tissues in grafted nude mice, compared for benchmarking to the same conjugate tagged with 68Ga. Extension to treatment trials with the 149Tb alpha emitter should follow as soon as such batch production and delivery can start. Alpha emitters are entering the body and kill much more cancer cells within a short range, hence without damaging healthy tissues or cells. Localized treatment results in a lower rate of metastasis and it is also useful in cases of cancers that can’t be treated with external beam radiation or surgically removed. Bioconjugates with alpha emitters can target even undetected metastasis, which could not be treated by external beam irradiation or surgical interventions.

CERN-MEDICIS facility will produce small batches of up to 500MBq of carrier-free isotopes suited for fundamental and pre-clinical research in medicine. This will be achieved by constructing suitable infrastructures to handle open radioactive sources. It will be an extension of the present ISOLDE class A laboratory, in which a dedicated isotope mass-separator and dedicated laboratories will operate. By choosing just the right combination of target materials (like titanium, lead, ceramics a.o) and the appropriate method, the ISOLDE team produces a wide range of made-to-order radioactive isotopes. Innovative isotopes can be applied in three fields: first of all for medical imaging, secondly for cancer treatment and finally they can be used with tiny seeds that will be inserted and act  in a localized area around near the target. Another fingerprint of MEDICIS is the development of new medical protocols by combining in addition recent advancements in robotics and surgical techniques.

MEDICIS targets will be brought back in a dedicated hot cell with a mechanical conveyor. The conveyor is funded by the Knowledge Transfer Fund that also provided a dedicated technology-transfer officer specializing in life sciences. When the sample reaches the cell an operator will extract and purify the isotopes, which will be sent in batches to external medical-research laboratories.

The facility is designed in order to cope with possible future upgrades like the threefold increased proton intensity from Linac4 or the 2 GeV increased energy at PSB. Moreover, an important feature of MEDICIS is the multi-user capabilities, in line with discussions for future European infrastructures in nuclear physics and in the field of medical physics. Conceptual studies for MEDICIS clearly showed that the driver used for nuclear physics can also be used to extend the number of users always using the same beam. This is an important feature not only for CERN but also for next generation facilities that are discussed in the European Union.

The first part of activities will be fully dedicated to the production and shipping of radioisotopes to the clinical and research centres in the region,” says Thierry Stora. So far the Geneva University Hospital (HUG), the Lausanne University Hospital (CHUV) and the Swiss Institute for Experimental Cancer Research (ISREC) of the Swiss Federal Institute of Technology in Lausanne (EPFL) will use CERN’s isotopes. However the idea is to expand this strong core to create a larger network of laboratories in Europe and beyond. In this direction, MEDICIS will profit from ISOLDE’s existing network.

“More research and treatment facilities in the member states have already expressed their interest in collaborating with CERN,” says Stora. “Researchers from the biomedical field are keen to share the diverse technical expertise we have at CERN, which is required to produce radioisotopes”. A big challenge for the MEDICIS project is to broaden the MEDICIS community in order to include not only physicists but also biologists, chemists, medical doctors. Opening to new disciplines is a key to success since they can contribute with new ideas for future projects and potential applications. For example, medical doctors or biochemists can help physicists to grasp a fundamental understanding of the mechanism of cancer and open new paths in MEDICIS research.

The MEDICIS project crystallizes CERN’s support in an activity that dates back to the 90s, when researchers from the ISOLDE collaboration had the first discussions with Geneva’s Cantonal Hospital. As Maria Borge, spokesperson of ISOLDE, says: “CERN has institutionally recognized something that has been on and off for almost 20 years”. Past activities at ISOLDE were to a large extend driven by H. Ravn from the target group and G Beyer from Geneva's Hospital. Systematic studies were carried out with radiolanthanides collected at ISOLDE and studies on small animals followed in Geneva. Biodistribution studies were carried out on tumor bearing mice to find out the best complexing chemical, a so-called chelator, to localize the radioligand in the tumor and minimize uptake in healthy organs. The most notable result was certainly the production and purification of the alpha emitter Terbium 149 (149Tb) in quantities required for animal studies. It was complemented with 152Tb to provide the associated functional cancer tissues imaging by PET scanner. Today this is known as theranostic pairs. The 149Tb alpha emitter showed killing action at a single cancer cell level. This pioneering study has been recently extended with other Terbium isotopes displaying complementary radiation properties.

The MEDICIS project is financed by CERN and counts on financial and in-kind donations from private foundations and from KU Leuven University in Belgium. Civil works will be completed by the end of 2013. The scientific installations are planned to be completed in 2015 and will include a radiochemical laboratory.