Rhenium and Technetium-oxo Complexes with Thioamide Derivatives of Pyridylhydrazine Bifunctional Chelators Conjugated to the Tumour Targeting Peptides Octreotate and Cyclic-RGDfK

Inorg Chem. 2017 Aug 21;56(16):9725-9741. doi: 10.1021/acs.inorgchem.7b01247. Epub 2017 Aug 2.

Abstract

This research aimed to develop new tumor targeted theranostic agents taking advantage of the similarities in coordination chemistry between technetium and rhenium. A γ-emitting radioactive isotope of technetium is commonly used in diagnostic imaging, and there are two β- emitting radioactive isotopes of rhenium that have the potential to be of use in radiotherapy. Variants of the 6-hydrazinonicotinamide (HYNIC) bifunctional ligands have been prepared by appending thioamide functional groups to 6-hydrazinonicotinamide to form pyridylthiosemicarbazide ligands (SHYNIC). The new bidentate ligands were conjugated to the tumor targeting peptides Tyr3-octreotate and cyclic-RGD. The new ligands and conjugates were used to prepare well-defined {M═O}3+ complexes (where M = 99mTc or natRe or 188Re) that feature two targeting peptides attached to the single metal ion. These new SHYNIC ligands are capable of forming well-defined rhenium and technetium complexes and offer the possibility of using the 99mTc imaging and 188/186Re therapeutic matched pairs.

MeSH terms

  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Drug Stability
  • Hydrazines / chemistry
  • Ligands
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Pyridines / chemistry
  • Rhenium / chemistry*
  • Semicarbazones / chemical synthesis*
  • Semicarbazones / chemistry
  • Theranostic Nanomedicine
  • Thioamides / chemistry

Substances

  • Coordination Complexes
  • Hydrazines
  • Ligands
  • Peptides, Cyclic
  • Pyridines
  • Semicarbazones
  • Thioamides
  • cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
  • octreotate, Tyr(3)-
  • Rhenium