[68Ga]Ga-Pentixafor for PET Imaging of Vascular Expression of CXCR-4 as a Marker of Arterial Inflammation in HIV-Infected Patients: A Comparison with 18F[FDG] PET Imaging

Abstract

People living with human immunodeficiency virus (PLHIV) have excess risk of atherosclerotic cardiovascular disease (ASCVD). Arterial inflammation is the hallmark of atherogenesis and its complications. In this study we aimed to perform a head-to-head comparison of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and Gallium-68 pentixafor positron emission tomography/computed tomography [68Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV. We prospectively recruited human immunodeficiency virus (HIV)-infected patients to undergo [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT within two weeks of each other. We quantified the levels of arterial tracer uptake on both scans using maximum standardized uptake value (SUVmax) and target–background ratio. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans. A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection and mean CD+ T-cell count of the study population were 71.08 ± 37 months and 522.17 ± 260.33 cells/µL, respectively. We found a high level of agreement in the quantification variables obtained using [18F]FDG PET and [68Ga]Ga-pentixafor PET. There is a good level of agreement in the arterial tracer quantification variables obtained using [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [68Ga]Ga-pentixafor may be applied in the place of [18F]FDG PET/CT for the quantification of arterial inflammation.

Imaging findings and clinical relevance of [68Ga]Ga -pentixafor PET in atherosclerosis: A systematic review

“…Cardiovascular risk factors included in the study included smoking, hypertension, dyslipidemia, diabetes, C-reactive protein (CRP) (≥ 3 mg/L), obesity, family history of cardiovascular disease and history of cardiovascular diseases. One study [10] reported only imaging outcome metrics and 5 studies [9,[11][12][13][14] reported imaging outcome metrics and clinical correlation metrics. Lawal et al [10] reported imaging outcome indicators of atherosclerotic lesion uptake of [ 68 Ga]Ga -pentixafor and [ 18 F]-FDG; Lu et al [9] reported imaging outcome indicators of lesion uptake of [ 68 Ga]Ga -pentixafor and [ 18 F]-FDG and correlation indicators of tracer uptake with cardiovascular risk factors; Kircher et al [11] reported imaging outcome indicators of lesion uptake of [ 68 Ga]Ga -pentixafor and [ 18 F]-FDG and correlation indicators of tracer uptake with plaque calci cation; Li et al [12,13] reported imaging outcome indicators of lesion uptake of [ 68 Ga]Ga -pentixafor and correlation indicators of tracer uptake with cardiovascular risk factors; Weiberg et al [14] reported imaging outcome indicators of lesion uptake [ 68 Ga]Ga -pentixafor and also reported correlation indicators of tracer uptake with cardiovascular risk factors, correlation indicators of tracer uptake with plaque calci cation and correlation indicators of cardiovascular risk factors with plaque calci cation.…”

“…Quality evaluation was performed with the QUADAS-2 tool. Risk of bias: for case selection, 5 studies [9,10,11,13,14] were medium risk, with the main risk arising from continuity or randomization of patient inclusion; for trials to be evaluated, 1 study [13] was high risk and 5 studies [9][10][11][12]14] were medium risk, with the main risk arising from the implementation of blinding and the determination of thresholds; for gold standard 4 studies [10,[12][13][14] were medium risk, with the main risk arising from the implementation of the blinding method; for case, ow and progression, 2 studies [12,13] were high risk and 1 study [14] was a medium risk, with the main risk arising from the completeness of the case inclusion analysis and the appropriate interval. All studies had a low risk of clinical applicability.…”

“…Year Country Prospective Age BMI kg/m 2 Time interval Lu [9] 2022 Austria China United States of America N 68±10 27.1 1 W Lawal [10] 2020 SouthAfrica Nigeria Germany Y 44.67±7.62 24.18±3.45 2 D…”

Potential novel imaging targets of inflammation in cardiac sarcoidosis

“…Clinical Data First used in hematologic malignancies, 94 68 Ga-Pentixafor has been used for imaging of atherosclerosis in the carotid arteries, 93,127 aorta, 96 and coronary arteries. 97 Identification of inflammatory areas of the myocardium post-myocardial infarction have been described both ex vivo 98 and in vivo.…”

“…99 Data suggest that there is good correlation between 18 F-FDG-PET-positive and 68 Ga-Pentixafor-positive areas when evaluating atherosclerosis. 127 While there is currently no published report of CXCR4 used in clinical imaging of sarcoidosis, CXCR4 could become a viable tracer target as it has been implicated in granuloma formation and macrophage-mediated inflammation. 128 It has also been used for visualization of inflammation of cardiac atherosclerotic plaques 97 which have generally lower inflammatory cell counts than sarcoid granulomassuggesting 68 Ga-Pentixafor could have good sensitivity for cardiac sarcoidosis.…”