New PET Centre for Brain Research
A new PET Centre for brain research has been established on campus at Jülich. Here, scientists investigate the structure and function of the healthy and diseased human brain and develop methods of diagnosing and treating neurological and psychiatric disorders. They use the latest procedures and techniques in the field of imaging as well as for fabricating and applying highly specific radiopharmaceuticals and contrast media. The new PET Centre is the culmination of more than 30 years of successful PET research at Jülich. It focuses on fundamental neuroscientific research with an emphasis on transferring current research findings to clinical applications. The PET Centre is an important new cornerstone of brain research at Jülich. On three storeys, it unites research with application, and combines them with the key competencies of Forschungszentrum Jülich in the fields of medical imaging and pharmaceutical radiochemistry.
The architectural design of the PET Centre follows the function of the building with each of its three storeys dedicated to different levels of research: development, testing and application. In the basement, researchers develop and modify radiotracers. On the ground floor, preclinical testing verifies whether the diagnostic and therapeutic agents are safe for application. In the clinical wing on the first floor, test subjects and patients participate in clinical trials with these substances. All process steps, tests and trials are subject to high quality and safety standards and the principles of good manufacturing and medical practice (GMP).
Development of radiotracers (level 1)
Radiotracers – short-lived radioactively labelled molecules – are produced in the basement. They are essential for investigating, diagnosing and treating diseases of the brain. Using these molecules as "scouts", different techniques allow drugs and other substances to be localized to within a millimetre in the brain of a patient. When they are used in positron emission tomography (PET), for example, they make metabolic processes in the brain visible. Researchers can then pinpoint where pharmaceuticals are effective, identify the destinations of neurotransmitters in the brain, as well as monitor tumour growth and pathological deposits in the brain.
Only very small amounts of these radioactively labelled substances with very short half-lives of between a few minutes and a few hours are actually used. The radiation exposure of a normal PET examination is comparable to that of X-ray examinations, which is around two to three times higher than the natural background radiation that humans are exposed to every year.
Forschungszentrum Jülich produces its own radiotracers using short-lived radionuclides, which are created especially for this purpose in the newly installed cyclotron in the PET Centre. The proximity of the cyclotron to where the patients are treated is particularly important when radiotracers with a half-life of an hour or less are used because such substances cannot be transported over long distances.
The experts working at the Institute of Neuroscience and Medicine – Nuclear Chemistry (INM-5) don't just produce radiotracers, they also develop new ones. Around 25 years ago, for example, scientists at Jülich discovered and patented a ground-breaking synthesis technique for one of the most important PET markers (18FDG – fluorine deoxyglucose). Today, some two million patients throughout the world benefit from this technique. In 2009, scientists at Forschungszentrum Jülich achieved another breakthrough in the production of an important substance (18-fluorodopa) which can be used to diagnose Parkinson's disease, in patients with brain tumours, and to search for certain tumours in the body. Industrial partners also come to Jülich to have their drugs and the modes of action labelled, tested and refined with the methods.
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Preclinical testing (level 2)
The ground floor of the PET Centre is dedicated to the preclinical testing of the new substances. The "preclinical evaluation platform" located here is operated by the Institute of Neuroscience and Medicine – Molecular Organization of the Brain (INM-2). Here, scientists test how safe the new active pharmaceutical ingredients (APIs) are by investigating their distribution in the body, any resulting radiation exposure, the necessary dosage and the metabolization of the drug candidates. Some of these tests are prescribed by the legal requirements of the German Pharmaceuticals Act as well as by the relevant European and national guidelines, and must be conducted before new substances can be used on humans. Only when tests have verified that these substances are safe for use and are not harmful to health can the next steps be taken, and clinical trials can then begin on humans.
This storey is also equipped with special imaging devices for small animals: a 7 tesla magnetic resonance imaging (MRI) scanner and a combined PET-computed tomography (PET-CT) device. These devices enable non-invasive brain examinations of animals to be conducted under the same conditions as those planned for future examinations on test subjects and patients if the animal tests prove successful. The direct methodological comparability ensures excellent transferability to humans. The measurements are non-invasive, making them an innovative and non-intrusive method of performing prescribed experiments in the area of drug research.
The preclinical evaluation platform is simultaneously an important cornerstone of the API research initiative launched by the Helmholtz Association in 2012 and provides six other Helmholtz centres with access to the facility to test new API candidates.
Clinical ward (level 3)
The first floor of the PET Centre is home to a state-of-the-art clinical ward, where tests can be performed on test subjects and patients can be diagnosed and treated. This area is equipped with a 3 tesla MRI scanner and a combined PET-computed tomography (PET-CT) device of the latest generation. The ward is where the legally prescribed multistage trials for drug development are conducted to verify that new drug candidates are safe and effective (referred to as phases 1 to 3 of clinical testing). In addition, the ward offers an ideal setting for clinical trials on test subjects. These trials are conducted by the Institute of Neuroscience and Medicine in cooperation with its scientific and clinical partners in line with Jülich’s focus on brain research.
Industrial cooperation partners can also make use of the innovative imaging techniques as an integral part of their drug testing strategies. This could apply to certain aspects of drug testing such as establishing dosing regimens, as well as basic issues such as molecular precision, e.g. in the case of neurological and psychiatric disorders.
The clinical ward is open to all of INM's partner institutes for research projects. Cooperations at the Jülich Institute of Neuroscience and Medicine also comprise numerous clinical trials – particularly with neighbouring university hospitals in Aachen, Bonn, Cologne and Düsseldorf – and include the development of brain tumour diagnostics with University Hospital Aachen and research work on the diagnosis of multiple sclerosis with Düsseldorf University Hospital.
In the field of fundamental neuroscientific research, the new infrastructure will consolidate the existing research cooperation with Harvard Medical School in Boston, which focuses on the basic mechanisms of regulating the sleep-wake cycle as well as disruptions to these mechanisms in diseases of the central nervous system (CNS).