Imaging Inflammation in Atherosclerosis with CXCR4-directed ⁶⁸Ga-Pentixafor PET/CT - Correlation with ¹⁸F-FDG PET/CT

Purpose: C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed on the surface of macrophages and various other cell types involved in atherosclerosis. First pilot studies with ⁶⁸Ga-Pentixafor, a novel CXCR4-directed positron emission tomography (PET) tracer, have demonstrated the feasibility of non-invasive inflammation imaging within atherosclerotic plaques. The aim of this study was to investigate the performance of ⁶⁸Ga-Pentixafor PET/computed tomography (CT) for imaging atherosclerosis in comparison to ¹⁸F-FDG PET/CT, the current standard in nuclear inflammation imaging.

Methods: Ninety-two patients (37 females and 55 males; mean age 62 ± 10 years) underwent ⁶⁸Ga-Pentixafor and ¹⁸F-FDG PET/CT examinations for staging of oncologic diseases. In a total of 652 corresponding atherosclerotic lesions, respective tracer uptakes were measured and arterial target-to-background ratios (TBR) calculated. Uptake values were then correlated and compared to the degree of arterial calcification as quantified in CT.

Results: TBR of both PET tracers showed a moderate positive correlation (r = 0.28; p < 0.01) with ⁶⁸Ga-Pentixafor demonstrating significantly higher TBR than ¹⁸F-FDG (1.8 ± 0.5 vs. 1.4 ± 0.4; p < 0.01). The degree of plaque calcification correlated inversely with both ⁶⁸Ga-Pentixafor and ¹⁸F-FDG uptake (r = -0.38 vs. r = -0.31, both p < 0.00001), respectively.

Conclusions: Non-invasive PET/CT imaging of atherosclerotic plaques using ⁶⁸Ga-Pentixafor features a better target-to-background contrast than ¹⁸F-FDG. Given that ⁶⁸Ga-Pentixafor uptake is lowest in severely calcified plaques that are considered less susceptible to rupture, CXCR4-directed PET/CT might prove a useful tool for identification and monitoring of high-risk patients.