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Hyafil, Fabien; Pelisek, Jaroslav; Laitinen, Iina; Schottelius, Margret; Mohring, Miriam; Döring, Yvonne; Vorst, Emiel P. C. van der; Kallmayer, Michael; Steiger, Katja; Poschenrieder, Andreas; Notni, Johannes; Fischer, Johannes; Baumgartner, Christine; Rischpler, Christoph; Nekolla, Stephan G.; Weber, Christian; Eckstein, Hans-Henning; Wester, Hans-Jürgen; Schwaiger, Markus (2017): Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer Ga-68-Pentixafor for PET. In: Journal of Nuclear Medicine, Vol. 58, No. 3: pp. 499-506
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Abstract

Ga-68-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of Ga-68-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of I-125-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of Ga-68-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR 5 1.95 +/- 0.51 vs. 1.22 +/- 0.25 and mean TBR 5 1.24 +/- 0.38 vs. 0.96 +/- 0.37, respectively;P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced I-125-pentixafor uptake in atherosclerotic plaques by approximately 40%. I-125-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r(2) = 0.61;P < 0.05). Conclusion: Ga-68-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to F-18-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.