The 18-kDa Translocator Protein PET Tracers as a Diagnostic Marker for Neuroinflammation: Development and Current Standing

Abstract

Translocator protein (TSPO, 18 kDa) is an evolutionary, well-preserved, and tryptophan-rich 169-amino-acid protein which localizes on the contact sites between the outer and inner mitochondrial membranes of steroid-synthesizing cells. This mitochondrial protein is implicated in an extensive range of cellular activities, including steroid synthesis, cholesterol transport, apoptosis, mitochondrial respiration, and cell proliferation. The upregulation of TSPO is well documented in diverse disease conditions including neuroinflammation, cancer, brain injury, and inflammation in peripheral organs. On the basis of these outcomes, TSPO has been assumed to be a fascinating subcellular target for early stage imaging of the diseased state and for therapeutic purposes. The main outline of this Review is to give an update on dealing with the advances made in TSPO PET tracers for neuroinflammation, synchronously emphasizing the approaches applied for the design and advancement of new tracers with reference to their structure-activity relationship (SAR).

Figure 1

Schematic representation of various TSPO functions.

Figure 2

Schematic diagram demonstrating cholesterol metabolism in steroidogenic cells.

Figure 3

Sequential categorization of PET Tracers.

Figure 4

First generation TSPO tracers.

Figure 5

Second generation TSPO tracers.

Figure 5

Second generation TSPO tracers.

Figure 6

Structural view of new generation PET tracers for TSPO.