title: A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury.
abstract: Sphingosine-1-phosphate receptor 1 (S1PR1) is highly expressed in vascular smooth muscle cells from intimal lesions. PET imaging using S1PR1 as a biomarker would increase our understanding of its role in vascular pathologies including in-stent restenosis.
  
  
  
  The S1PR1 compound TZ3321 was synthesized for in vitro characterization and labeled with Carbon-11 for in vivo studies. The biodistribution of [11C]TZ3321 was evaluated in normal mice; microPET and immunohistochemistry (IHC) studies were performed using a murine femoral artery wire-injury model of restenosis.
  
  
  
  The high potency of TZ3321 for S1PR1 (IC50= 2.13 ± 1.63 nM), and high selectivity (>1000 nM) for S1PR1 over S1PR2 and S1PR3 were confirmed. Biodistribution data revealed prolonged retention of [11C]TZ3321 in S1PR1-enriched tissues. MicroPET imaging of [11C]TZ3321 showed higher uptake in the wire-injured arteries of ApoE-/-mice than in injured arteries of wild-type mice (SUV 0.40 ± 0.06 vs 0.28 ± 0.04, n = 6, P < .001); FDG-PET showed no difference (SUV 0.98 ± 0.04 vs 0.94 ± 0.01, n = 6, P > .05). Post-PET autoradiography showed >4-fold higher [11C]TZ3321 retention in the injured artery of ApoE-/-mice than in wild-type mice. Subsequent IHC staining confirmed higher expression of S1PR1 in the neointima of the injured artery of ApoE-/-mice than in wild-type mice.
  
  
  
  This preliminary study supports the potential use of PET for quantification of the S1PR1 expression as a biomarker of neointimal hyperplasia.
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Hongjun
authors: H
authors: Jin
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Hao
authors: H
authors: Yang
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Hui
authors: H
authors: Liu
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Yunxiao
authors: Y
authors: Zhang
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Xiang
authors: X
authors: Zhang
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Adam J
authors: AJ
authors: Rosenberg
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Yongjian
authors: Y
authors: Liu
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA.
authors: Suzanne E
authors: SE
authors: Lapi
authors: Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St. Louis, MO, 63110, USA. tuz@mir.wustl.edu.
authors: Zhude
authors: Z
authors: Tu
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D006083:Graft Occlusion, Vascular / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000081025:Sphingosine-1-Phosphate Receptors; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; C000615233:Carbon-11; D019275:Radiopharmaceuticals; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors
keywords: MicroPET imaging; atherosclerosis; biodistribution; diagnostic and prognostic application; inflammation