Preclinical evaluation of an 18F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis

Biochem Biophys Res Commun. 2024 Apr 9:703:149650. doi: 10.1016/j.bbrc.2024.149650. Epub 2024 Feb 7.

Abstract

Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE-/-) mice. The aortas ApoE-/- mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE-/- mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE-/- mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE-/- mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE-/- mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo.

Keywords: Aptamer; Atherosclerosis; Positron emission tomography; Tenascin-C.

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Atherosclerosis* / metabolism
  • Azo Compounds*
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Fluorine Radioisotopes*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotides / metabolism
  • Plaque, Atherosclerotic* / pathology
  • Positron-Emission Tomography / methods
  • Tenascin / metabolism
  • Tissue Distribution

Substances

  • Fluorine-18
  • Tenascin
  • oil red O
  • Oligonucleotides
  • Apolipoproteins E
  • Azo Compounds
  • Fluorine Radioisotopes