Isotopes for precision medicine

15 January 2018

The CERN-MEDICIS facility has produced its first radioisotopes for medical research.

The use of radioisotopes to treat cancer goes back to the late 19th century, with the first clinical trials taking place in France and the US at the beginning of the 20th century. Great strides have been made, and today radioisotopes are widely used by the medical community. Produced mostly in dedicated reactors, radioisotopes are used in precision medicine, both to diagnose cancers and other diseases, such as heart irregularities, as well as to deliver very small radiation doses exactly where they are needed to avoid destroying the surrounding healthy tissue.

However, many currently available isotopes do not combine the most appropriate physical and chemical properties and, in the case of certain tumours, a different type of radiation could be better suited. This is particularly true of the aggressive brain cancer glioblastoma multiforme and of pancreatic adenocarcinoma. Although external beam gamma radiation and chemotherapy can improve patient survival rates, there is a clear need for novel treatment modalities for these and other cancers.

On 12 December, a new facility at CERN called MEDICIS produced its first radioisotopes: a batch of terbium (155Tb), which is part of the 149/152/155/161Tb family considered a promising quadruplet suited for both diagnosis and treatment. MEDICIS is designed to produce unconventional radioisotopes with the right properties to enhance the precision of both patient imaging and treatment. It will expand the range of radioisotopes available – some of which can be produced only at CERN – and send them to hospitals and research centres in Switzerland and across Europe for further study.

Initiated in 2010 by CERN with contributions from the Knowledge Transfer Fund, private foundations and partner institutes, and also benefitting from a European Commission Marie Skłodowska-Curie training grant titled MEDICIS-Promed, MEDICIS is driven by CERN’s Isotope Mass Separator Online (ISOLDE) facility. ISOLDE has been running for 50 years, producing 1300 different isotopes from 73 chemicals for research in many areas including fundamental nuclear research, astrophysics and life sciences.

Although ISOLDE already produces isotopes for medical research, MEDICIS will more regularly produce isotopes with specific types of emission, tissue penetration and half-life – all purified based on expertise acquired at ISOLDE. This will allow CERN to provide radioisotopes meeting the requirements of the medical research community as a matter of course.

ISOLDE directs a high-intensity proton beam from the Proton Synchrotron Booster onto specially developed thick targets, yielding a large variety of atomic fragments. Different devices are used to ionise, extract and separate nuclei according to their masses, forming a low-energy beam that is delivered to various experimental stations. MEDICIS works by placing a second target behind ISOLDE’s: once the isotopes have been produced on the MEDICIS target, an automated conveyor belt carries them to a facility where the radioisotopes of interest are extracted via mass separation and implanted in a metallic foil. The final product is then delivered to local research facilities including the Paul Scherrer Institute, the University Hospital of Vaud and Geneva University Hospitals.

Clinical setting

Once in a medical-research environment, researchers dissolve the isotope and attach it to a molecule, such as a protein or sugar, which is chosen to target the tumour precisely. This makes the isotope injectable, and the molecule can then adhere to the tumour or organ that needs imaging or treating. Selected isotopes will first be tested in vitro, and in vivo by using mouse models of cancer. Researchers will test the isotopes for their direct effect on tumours and when they are coupled to peptides with tumour-homing capacities, and establish new delivery methods for brachytherapy using stereotactic or robotic-assisted surgery in large-animal models for their capacity to target glioblastoma or pancreatic adenocarcinoma or neuroendocrine tumour cells.

MEDICIS is not just a world-class facility for novel radioisotopes. It also marks the entrance of CERN into the growing field of theranostics, whereby physicians verify and quantify the presence of cellular and molecular targets in a given patient with a diagnostic radioisotope, before treating the disease with the therapeutic radioisotope. The prospect of a dedicated facility at CERN for the production of innovative isotopes, together with local leading institutes in life and medical sciences and a large network of laboratories, gives MEDICIS an exciting scientific programme in the years to come. It is also a prime example of the crossover between fundamental physics research and health applications, with accelerators set to play an increasing role in the production of life-changing medical isotopes.

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