Development of 99mTc-labeled trivalent isonitrile radiotracer for folate receptor imaging

Bioorg Med Chem. 2019 May 15;27(10):1925-1931. doi: 10.1016/j.bmc.2019.04.013. Epub 2019 Apr 10.

Abstract

Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent 99mTc(CO)3-labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for FR target imaging. [99mTc]Tc-10 was HPLC purified (>98% chemical purity) and evaluated in vitro and in vivo as a potential agent for targeting FR-positive KB cells. [99mTc]Tc-10 is a hydrophilic compound with partition coefficient of -2.90 ± 0.13 that showed high binding affinity (0.04 ± 0.002 nM) in vitro. High accumulation and retention of [99mTc]Tc-10 (5.32 ± 2.99% ID/g) was observed in mice with KB tumors at 4 h after injection through the tail vein, which was significantly inhibited by co-injection of free folic acid (FA). SPECT (single photon emission tomography)/CT results were in accordance with biodistribution data at all time points.

Keywords: Folic acid; Isocyanide; Technetium-99m; Tricarbonyl; Trivalent probe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Stability
  • Folate Receptors, GPI-Anchored / chemistry
  • Folate Receptors, GPI-Anchored / metabolism*
  • Humans
  • KB Cells
  • Mice
  • Mice, Nude
  • Neoplasms / diagnostic imaging
  • Nitriles / blood
  • Nitriles / chemistry*
  • Nitriles / metabolism
  • Organotechnetium Compounds / chemistry
  • Radiopharmaceuticals / blood
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Transplantation, Heterologous

Substances

  • Folate Receptors, GPI-Anchored
  • Nitriles
  • Organotechnetium Compounds
  • Radiopharmaceuticals