Al18 F labeled sulfonamide-conjugated positron emission tomography tracer in vivo tumor-targeted imaging

J Cell Biochem. 2019 Oct;120(10):17006-17014. doi: 10.1002/jcb.28961. Epub 2019 May 26.

Abstract

An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high-resolution images in vivo. In this work, the aim was to evaluate the application of Al18 F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid containing sulfonamide group (18 F-Al-NOTA-SN) as a potential tumor-targeting signal-enhanced radioactive tracer in PET. SN as a tumor-targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18 F and AlCl3 to produce a compound 18 F-Al-NOTA-SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18 F-Al-NOTA-SN possessed low cell cytotoxicity and uptake to COS-7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA-MB-231, HepG2, and HeLa tumor cells in vitro. Moreover, 18 F-Al-NOTA-SN showed good tumor-targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18 F-Al-NOTA-SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor-targeting signal-enhanced radioactive tracer in PET.

Keywords: 18F-labeled tracer; NOTA; positron emission computed tomography; sulfonamide; tumor-targeting property.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Female
  • Gallium Radioisotopes / chemistry*
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Heterocyclic Compounds, 1-Ring / chemical synthesis
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Positron-Emission Tomography / methods*
  • Sulfonamides / chemistry*
  • Tissue Distribution
  • Uterine Neoplasms / diagnostic imaging*
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Sulfonamides
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid