Inflammation in the vascular wall plays an important role in the pathophysiology of atherosclerosis, including the development of plaque, plaque destabilization, and rupture. In the carotid artery, a plaque may become symptomatic when it suddenly swells or promotes the formation of thrombosis and downstream embolism. As an example, stenosing atherosclerotic disease in the carotid artery is present in a large number of stroke patients [
1]. In addition, large vessel vasculitis, such as Takayasu’s arteritis and Giant Cell arteritis, is characterized by a cellular immune response involving T cells and macrophages [
2]. These conditions are challenging from a diagnostic perspective, because arteritis affecting the aortic arch may delay the clinical diagnosis of potentially life-threatening alterations in hemodynamic parameters.
In this context, a noninvasive method of detecting inflammatory activity, such as the accumulation of macrophages, in arteries would be of great clinical value to orient prognosis, direct therapy, and assess novel therapies. While standard imaging modalities can quantify the degree of stenosis and the thickness of an inflamed arterial wall, they cannot directly identify an inflammatory component. The positron emission tomography (PET) tracer [
18F]-FDG, is clinically used to diagnose vascular inflammation [
3,
4] but may also aspecifically accumulate in any metabolically active tissues or cells. Radiopharmaceuticals targeting 18 kDa translocator protein (TSPO), a protein heavily expressed in macrophages, may identify the presence of inflammation in the vascular wall more specifically and perhaps earlier. Indeed, recent findings underscored the interest of TSPO imaging in inflamed plaque, because TSPO co-localized with a subset of CD11b + macrophages which are recruited in advanced atherosclerotic lesions [
5]. Pilot comparative studies suggest the superiority of TSPO-based radiopharmaceutical to image vulnerable plaque vs [
18F]-FDG [
6]. For instance, ex vivo autoradiography with [
3H]-PK11195 suggests that TSPO-imaging of macrophages in atherosclerotic plaque may be feasible [
7]. In humans, PET imaging with [
11C]-(
R)-PK11195 correlated well with [
3H]-PK11195 binding in ex vivo samples [
8]. Additionally, PET imaging with [
11C]-(
R)-PK11195 differentiated symptomatic from asymptomatic patients with atherosclerosis [
8]. However, PK11195 has moderate affinity for TSPO and low specific binding [
9]. Thus, recently developed TSPO radioligands with higher affinity for the target [
10] may be more useful for in vivo imaging of vascular wall inflammation. Among these recently developed radioligands, [
18F]-PBR06 has been successfully used in mice to image macrophage infiltration in atherosclerotic plaques, but no human imaging has been performed so far [
11].
This study sought to assess the feasibility of using second generation TSPO imaging to identify vascular inflammation by performing [18F]-PBR06 autoradiography on surgical samples collected from unstable carotid plaques. In addition, patients with inflamed carotid plaques and large vessel vasculitis were scanned using one of two TSPO tracers: [11C]-PBR28 and [18F]-PBR06.