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

Abstract

C-X-C motif chemokine receptor 4 (CXCR4) is expressed on the surface of various cell types involved in atherosclerosis, with a particularly rich receptor expression on macrophages and T cells. First pilot studies with ⁶⁸Ga-pentixafor, a novel CXCR4-directed PET tracer, have shown promise to noninvasively image inflammation within atherosclerotic plaques. The aim of this retrospective study was to investigate the performance of ⁶⁸Ga-pentixafor PET/CT for imaging atherosclerosis in comparison to ¹⁸F-FDG PET/CT. <b>Methods:</b> Ninety-two patients (37 women and 55 men; mean age, 62 ± 10 y) underwent ⁶⁸Ga-pentixafor and ¹⁸F-FDG PET/CT for staging of oncologic diseases. In these subjects, lesions in the walls of large arteries were identified using morphologic and PET criteria for atherosclerosis (<i>n</i> = 652). Tracer uptake was measured and adjusted for vascular lumen (background) signal by calculation of target-to-background ratios (TBRs) by 2 investigators masked to the other PET scan. On a lesion-to-lesion and patient basis, the TBRs of both PET tracers were compared and additionally correlated to the degree of arterial calcification as quantified in CT. <b>Results:</b> On a lesion-to-lesion basis, ⁶⁸Ga-pentixafor and ¹⁸F-FDG uptake showed a weak correlation (<i>r</i> = 0.28; <i>P</i> < 0.01). ⁶⁸Ga-pentixafor PET identified more lesions (<i>n</i> = 290; TBR ≥ 1.6, <i>P</i> < 0.01) and demonstrated higher uptake than ¹⁸F-FDG PET (1.8 ± 0.5 vs. 1.4 ± 0.4; <i>P</i> < 0.01). The degree of plaque calcification correlated negatively with both ⁶⁸Ga-pentixafor and ¹⁸F-FDG uptake (<i>r</i> = -0.38 vs. -0.31, both <i>P</i> < 0.00001). <b>Conclusion:</b> CXCR4-directed imaging of the arterial wall with ⁶⁸Ga-pentixafor PET/CT identified more lesions than ¹⁸F-FDG PET/CT, with only a weak correlation between tracers. Further studies to elucidate the underlying biologic mechanisms and sources of CXCR4 positivity, and to investigate the clinical utility of chemokine receptor-directed imaging of atherosclerosis, are highly warranted.