Towards to hENT1-nucleoside transporter selective imaging agents. Synthesis and in vitro evaluation of the radiolabeled SAENTA analogues

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5151-4. doi: 10.1016/j.bmcl.2009.07.017. Epub 2009 Jul 9.

Abstract

Three new potential hENT(1) inhibitors suitable for labeling with PET/SPECT radioisotopes were prepared from an advanced intermediate 4. They were tested for their capability to inhibit binding of SAENTA-fluorescein to HL60 leukemia cells in flow cytometry assay and SAENTA-I (5) was determined to be the most active compound. (131)I-5 showed high hENT(1)-specific binding (up to 54% ID) to 6 from 7 tested tumor cell lines and was chosen for further in vivo study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / chemistry
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Cell Line, Tumor
  • Equilibrative Nucleoside Transporter 1 / metabolism*
  • Flow Cytometry
  • Fluorescent Dyes / chemistry
  • Humans
  • Iodine Radioisotopes / chemistry
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Thionucleosides / chemical synthesis
  • Thionucleosides / chemistry*

Substances

  • Benzamides
  • Equilibrative Nucleoside Transporter 1
  • Fluorescent Dyes
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • SLC29A1 protein, human
  • Thionucleosides
  • 5'-S-(2-aminoethyl)-N(6)-(4-nitrobenzyl)-5'-thioadenosine
  • Adenosine