PET Imaging of the Peripheral Benzodiazepine Receptor: Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders

Janine      Doorduin; Erik   F.J.   de Vries; Rudi   A.   Dierckx; Hans   C.   Klein

doi:10.2174/138161208786549443

Abstract

It is important to gain more insight into neurodegenerative diseases, because these debilitating diseases can not be cured. A common characteristic of many neurological diseases is neuroinflammation, which is accompanied by the presence of activated microglia cells. In activated microglia cells, an increase in the expression of peripheral benzodiazepine receptors (PBR) can be found. The PBR was suggested as a target for monitoring disease progression and therapy efficacy with positron emission tomograpy (PET). The PET tracer [ C]PK11195 has been widely used for PBR imaging, but the tracer has a high lipophilicity and high non-specific binding which makes it difficult to quantify uptake. Therefore, efforts are being made to develop more sensitive radioligands for the PBR. Animal studies have yielded several promising new tracers for PBR imaging, such as [ C]DAA1106, [ F]FEDAA1106, [ C]PBR28, [11C]DPA713 and [11C]CLINME. However, the potential of these new PBR ligands is still under investigation and as a consequence [ C]PK11195 is used so far to image activated microglia cells in neurological disorders. With [ C]PK11195, distinct neuroinflammation was detected in multiple sclerosis, Parkinson ’ s disease, encephalitis and other neurological diseases. Because neuroinflammation plays a central role in the progression of neurodegenerative diseases, anti-inflammatory drugs have been investigated for therapeutic intervention. Especially minocycline and cyclooxygenase inhibitors have shown in vivo anti-inflammatory, hence neuroprotective properties, that could be detected by PET imaging of the PBR with [ C]PK11195. The imaging studies published so far showed that the PBR can be an important target for monitoring disease progression, therapy response and determining the optimal drug dose.

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