RT Journal Article SR Electronic T1 Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer 68Ga-Pentixafor for PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 499 OP 506 DO 10.2967/jnumed.116.179663 VO 58 IS 3 A1 Fabien Hyafil A1 Jaroslav Pelisek A1 Iina Laitinen A1 Margret Schottelius A1 Miriam Mohring A1 Yvonne Döring A1 Emiel P.C. van der Vorst A1 Michael Kallmayer A1 Katja Steiger A1 Andreas Poschenrieder A1 Johannes Notni A1 Johannes Fischer A1 Christine Baumgartner A1 Christoph Rischpler A1 Stephan G. Nekolla A1 Christian Weber A1 Hans-Henning Eckstein A1 Hans-Jürgen Wester A1 Markus Schwaiger YR 2017 UL http://jnm.snmjournals.org/content/58/3/499.abstract AB 68Ga-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 68Ga-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 125I-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 68Ga-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 = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively; P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced 125I-pentixafor uptake in atherosclerotic plaques by approximately 40%. 125I-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 (r2 = 0.61; P < 0.05). Conclusion: 68Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to 18F-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.