Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: Preliminary comparative PET studies with [¹¹C]vinpocetine and [¹¹C]PK11195 in patients

Abstract 

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [¹¹C]vinpocetine and [¹¹C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage.

However, regional BP values for [¹¹C]vinpocetine were markedly higher than those for [¹¹C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [¹¹C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage.

The present findings (i) confirm earlier observations with [¹¹C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [¹¹C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [¹¹C]vinpocetine shows a number of characteristics favourable in comparison with [¹¹C]PK11195.

Keywords: Vinpocetine, PK11195, Peripheral benzodiazepine binding site, Glia, Positron emission tomography, Sclerosis multiplex