Malte Kircher1, Johannes Tran-Gia1, Luisa Kemmer1, Xiaoli Zhang2, Andreas Schirbel1, Rudolf A Werner1, Andreas K Buck1, Hans-Jürgen Wester3, Marcus Hacker4, Constantin Lapa5, Xiang Li2,4. 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. 2. Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 3. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany; and. 4. Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria. 5. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany lapa_c@ukw.de.
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. Methods: 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 (n = 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. Results: On a lesion-to-lesion basis, 68Ga-pentixafor and 18F-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). 68Ga-pentixafor PET identified more lesions (n = 290; TBR ≥ 1.6, P < 0.01) and demonstrated higher uptake than 18F-FDG PET (1.8 ± 0.5 vs. 1.4 ± 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both 68Ga-pentixafor and 18F-FDG uptake (r = -0.38 vs. -0.31, both P < 0.00001). Conclusion: 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.
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. Methods: 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 (n = 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. Results: On a lesion-to-lesion basis, 68Ga-pentixafor and 18F-FDG uptake showed a weak correlation (r = 0.28; P < 0.01). 68Ga-pentixafor PET identified more lesions (n = 290; TBR ≥ 1.6, P < 0.01) and demonstrated higher uptake than 18F-FDG PET (1.8 ± 0.5 vs. 1.4 ± 0.4; P < 0.01). The degree of plaque calcification correlated negatively with both 68Ga-pentixafor and 18F-FDG uptake (r = -0.38 vs. -0.31, both P < 0.00001). Conclusion: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.
Authors: Andrej Ćorović; Christopher Wall; Justin C Mason; James H F Rudd; Jason M Tarkin Journal: Curr Cardiol Rep Date: 2020-08-09 Impact factor: 3.955