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

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 Ga-68-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 Ga-68-pentixafor PET/CT for imaging atherosclerosis in comparison to F-18-FDG PET/CT. Methods: Ninety-two patients (37 women and 55 men; mean age, 62 +/- 10 y) underwent Ga-68-pentixafor and F-18-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 (n = 652). Tracer uptake was measured and adjusted for vascular lumen (background) signal by calculation of target-tobackground 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. Results: On a lesion-tolesion basis, esGa-pentixafor and F-18-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). Ga-68-pentixafor PET identified more lesions (n = 290; TBR 1.6, P < 0.01) and demonstrated higher uptake than F-18-FDG PET (1.8 0.5 vs. 1.4 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both (68)G-apentixafor and F-18-FDG uptake (r =-0.38 vs.-0.31, both P < 0.00001). Conclusion: CXCR4-directed imaging of the arterial wall with Ga-68-pentixafor PET/CT identified more lesions than F-18-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.