A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury.

Academic Article


  • BACKGROUND: 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. METHODS: 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. RESULTS: The high potency of TZ3321 for S1PR1 (IC 50 = 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. CONCLUSIONS: This preliminary study supports the potential use of PET for quantification of the S1PR1 expression as a biomarker of neointimal hyperplasia.
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  • MicroPET imaging, atherosclerosis, biodistribution, diagnostic and prognostic application, inflammation, Animals, Carbon Radioisotopes, Feasibility Studies, Female, Graft Occlusion, Vascular, Humans, Image Enhancement, Male, Metabolic Clearance Rate, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Diagnostic Techniques, Organ Specificity, Positron-Emission Tomography, Radiopharmaceuticals, Receptors, Lysosphingolipid, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution
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    Author List

  • Jin H; Yang H; Liu H; Zhang Y; Zhang X; Rosenberg AJ; Liu Y; Lapi SE; Tu Z
  • Start Page

  • 558
  • End Page

  • 570
  • Volume

  • 24
  • Issue

  • 2