C-X-C motif chemokine receptor 4-directed PET signal in the arterial tree is not consistently linked to calcified plaque burden and cardiovascular risk

Purpose: To establish the extent, distribution and frequency of in-vivo vessel wall [68Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). Methods: 65 oncological patients undergoing [Ga-68]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined. We then investigated associations of vessel wall uptake with CAP burden, cardiovascular risk (CVRF and European Society of Cardiology [ESC] SCORE2/SCORE2-OP risk chart) and image noise (determined by coefficient of variation [CoV] from unaffected liver parenchyma). Results: We identified 1292 sites of high focal [Ga-68]Ga-PentixaFor uptake (PentixaFor+ sites) in the vessel wall in 65/65 (100%) patients, with concomitant calcification in 385/1292 (29.8%) sites. There were no significant associations between vessel wall uptake and CAP burden (number of PentixaFor+ sites: r <= 0.18, P >= 0.14; PentixaFor+ TBR: r <= 0.08, P >= 0.54). The number of PentixaFor+ sites showed a moderate correlation with cardiovascular risk (ESC SCORE2/SCORE2-OP, r = 0.30; number of CVRF, r = 0.26; P = 0.04, respectively), but failed to reach significance for PentixaFor+ TBR (r <= 0.18, P >= 0.22). In univariable regression analysis, body mass index (odds ratio [OR] 1.08, 95%-confidence interval [CI] 1.02-1.14) and CoV (OR, 1.07; CI, 1.05-1.10) were linked to TBR and the number of PentixaFor+ sites (P < 0.01, respectively), while injected activity was only associated with the latter imaging parameter (OR, 0.99; CI, 0.98-1.00; P = 0.04). In multivariable regression, injected activity (OR, 1.00; CI, 0.99-1.00) and CoV (OR, 1.06; CI, 1.06-1.07) remained significantly associated with the number of PentixaFor+ sites (P < 0.01, respectively). CoV, however, was the only parameter significantly linked to PentixaFor+ TBR on multivariable analysis (OR, 1.02; CI, 1.01-1.03; P < 0.01). Conclusion: On a visual and quantitative level, high focal [Ga-68]Ga-PentixaFor uptake in the arterial tree was not consistently linked to vessel wall calcification or cardiovascular risk. Image noise, however, may account for a substantial portion of apparent vessel wall uptake.