PT  - JOURNAL ARTICLE
AU  - Kircher, Malte
AU  - Tran-Gia, Johannes
AU  - Kemmer, Luisa
AU  - Zhang, Xiaoli
AU  - Schirbel, Andreas
AU  - Werner, Rudolf A.
AU  - Buck, Andreas K.
AU  - Wester, Hans-Jürgen
AU  - Hacker, Marcus
AU  - Lapa, Constantin
AU  - Li, Xiang
TI  - Imaging Inflammation in Atherosclerosis with CXCR4-Directed <sup>68</sup>Ga-Pentixafor PET/CT: Correlation with <sup>18</sup>F-FDG PET/CT
AID  - 10.2967/jnumed.119.234484
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 751--756
VI  - 61
IP  - 5
4099  - http://jnm.snmjournals.org/content/61/5/751.short
4100  - http://jnm.snmjournals.org/content/61/5/751.full
SO  - J Nucl Med2020 May 01; 61
AB  - 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.