Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors

Molecules. 2021 Jul 28;26(15):4552. doi: 10.3390/molecules26154552.

Abstract

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specific tumor uptake. Compared with [99mTc]Tc-CN5FA, the tumor/muscle ratios of [99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99mTc complexes have potential as tumor imaging agents to target folate receptors.

Keywords: 99mTc; SPECT/CT imaging; folate receptor; isonitrile.

MeSH terms

  • Animals
  • Binding, Competitive
  • Diagnostic Imaging / methods*
  • Drug Stability
  • Folate Receptors, GPI-Anchored / genetics
  • Folate Receptors, GPI-Anchored / metabolism*
  • Folic Acid / chemistry*
  • Folic Acid / pharmacokinetics
  • Gene Expression
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • KB Cells
  • Kidney / diagnostic imaging*
  • Kidney / metabolism
  • Mice
  • Nitriles / chemistry*
  • Protein Binding
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Technetium / chemistry
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods*

Substances

  • Folate Receptors, GPI-Anchored
  • Nitriles
  • Radiopharmaceuticals
  • Technetium
  • Folic Acid