In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease

Abstract

Background: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28.

Results: All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants.

Conclusion: Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease.

Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .

Keywords: Atherosclerosis; Inflammation; PET/CT; TSPO; Vasculitis.

Conflict of interest statement

The authors have no conflict of interest to disclose, financial or otherwise.

Figures

Fig. 1

Immunohistochemistry scoring of h-caldemon, α-smooth muscle actin (α-SMA), CD45, CD3 and CD68 investigated in this study. α-SMA and h-caldesmon stains were used to quantify the percentage of the fibrous rupture of the tunica media of the muscular arteries CD45, CD3, and CD68 stains assessed the count of leukocytes, T lymphocytes, and macrophages per 10 high magnification (× 400) fields, respectively

Fig. 2

[18F]-PBR06 autoradiography at baseline (a) and after pre-incubation with cold [natF]-PBR06 (b) and HES anatomical sections (c) in a piece of carotid endarterectomy. A large atheromatous plaque with calcification invaded the intima and tunica media of the arterial wall (d, × 25). Immunohistochemistry showed destruction of the tunica media by the plaque (e, × 25), macrophage infiltration around the cholesterol clefts (f, × 25), and scattered T-lymphocytes (g, × 100) within the plaque. The brown bar in the upper left corner is a 1-mm scale bar

Fig. 3

Co-localization of [18F]-PBR06 and CD68 macrophages. a CD68 immunohistochemistry. b fused image of [18F]-PBR06 micro-imaging and CD68 staining

Fig. 4

Quantification of [18F]-PBR06 specific binding according to various areas of atheromatous plaque (whole plaque, macrophages, and smooth muscle compartment (SMC)) of all eight samples

Fig. 5

A representative [18F]-PBR06 PET/CT (A, C) scan and angio-CT (B, D) scan. No uptake was observed on the right carotid atheromatous plaque