Dutch Focus


The detrimental impact of brain disorders can be life changing. To better understand their causes, scientists are pioneering a new molecular imaging process, which is both economic and accessible. Using this method to visualise the operations of a glycoprotein present in the brain, they ultimately aim to design benign treatments, which modulate its potentially harmful functions


GMP facility for the production of PET tracers. (photo courtesy of prof. dr. J. Pruim)


multidisciplinary group, which includes radiochemists, pharmacologists, biologists, physicists, and physicians,” says Luurtsema. “We’re


collaborating with Dr. Bert


Windhorst from the VU University Medical Center of Amsterdam and Prof. Dr. Nicola Antonio Colabufo from the University in Bari, Italy, and have also forged relationships with partners in Brazil.” A comprehensive


infrastructure supports


their activities at the department of Nuclear Medicine and Molecular Imaging of


the


UMCG, including the latest PET-CT scanners,


in-house GMP- facilities for


synthesising tracers and a recently refurbished set of cyclotron units (particle accelerators used to produce radionuclides for PET diagnostics). “We strongly


suspect that the


functionality of the BBB is related to brain disorders,” says Luurtsema.


“If its


Enhancing molecular imaging to develop new treatments for brain disorders


There are as many neurons human brain as Milky Way.


in the


there are stars in the It’s not in the least bit


surprising, then, that within the inner space of our cerebra, mysterious biological processes that science cannot yet define occur. Although their physical symptoms are often discomfortingly visible, limitations of


the investigative often means that triggers delicate organ disorders, at a molecular level, requires


technology for brain are


difficult to discern. Prising secrets from this


high-


resolution examinations of live subjects, which has stimulated a need for new monitoring tools. “PET (Positron Emission Tomography) is


the current, ‘state of the art’ system used for analysing sensitive molecular activity within the brain. It uses scanner systems, which monitor radioactive tracers injected into a


subject, to generate


biological processes within


the body,” 24 in vivo – that


images of is,


explains Dr. Gert


Luurtsema. A specialist University


of Groningen,


from the University


Medical Center Groningen (UMCG), Luurtsema currently heads a STW project seeking to better understand and control the role of P-glycoprotein (P-gp)


in the


brain. P-gp is an efflux transporter, a protein which ejects harmful and toxic compounds from brain cells. Located at the protective blood brain barrier (BBB) and several peripheral organs, P-gp acts like a microscopic doorman, granting entry to benign


objects and molecules whilst


shielding the brain from perceived threats. Whilst widely acknowledged as playing a critical


role in developing the body’s


immunity to certain types of medicines, it is also now becoming recognised as a potential catalyst of brain sickness. Funded by a €500,000 budget across its


four year duration, the venture, launched in 2012,


unites a team of multinational


specialists at a European centre renowned for its expertise in PET technology. “It’s a


operations are disturbed, we believe that they


conditions


can become a causal like


factor in Alzheimer’s and


Parkinson’s disease. Inadequate clearance of peptides [an operation undertaken by the P-gp] could lead them to accumulate in the brain. This could, we propose, lead to toxic phenomena when they penetrate the BBB.” But, he admits, the researchers don’t entirely know how these mechanisms work in vivo. If these functions can be better understood, improved


diagnostics and


perhaps therapeutic treatments could be devised to address them. However, current imaging tools used to


examine brain functions are inadequate for the task. Carbon-11, a commonly used radionuclide for synthesizing a PET tracer, has a short half


life of


twenty minutes,


which curtails the duration of monitoring cycles. Moreover, this carbon-11 labelled tracer can only be used by PET facilities which possess an on-site cyclotron, as well as GMP compliant radiopharmaceutical production


configuration. “Developing


very specific fluorine-18 labelled tracers that are specifically carried by P-gp, and no other transporters, has been absolutely critical for us and is therefore the focus of this project,” says Luurtsema. “These fluorine-18 labelled tracers must


also be stable once in vivo, and remain so throughout


an entire PET scan. Their radiochemistry must be reliable, and the Insight Publishers | Projects


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