Toward hypoxia-selective rhenium and technetium tricarbonyl complexes.

Abstract

With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium(I) and rhenium(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated p-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A (99m)Tc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse.

• Authors: Andrea J North, David J Hayne, Christine Schieber, Katherine Price, Anthony R White, Peter J Crouch, Angela Rigopoulos, Graeme J O'Keefe, Henri Tochon-Danguy, Andrew M Scott, Jonathan M White, Uwe Ackermann, Paul S Donnelly
• Journal: Inorganic chemistry (Inorg Chem) Vol. 54 Issue 19 Pg. 9594-610 (Oct 05 2015) ISSN: 1520-510X [Electronic] United States
• PMID: 26375592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Organometallic Compounds
• Rhenium
• Technetium

Topics

• Animals
• Cell Line, Tumor
• Diagnostic Imaging
• Electrochemical Techniques
• HeLa Cells
• Humans
• Hypoxia
• Ligands
• Luminescence
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Fluorescence
• Models, Molecular
• Molecular Structure
• Organometallic Compounds (chemical synthesis, chemistry, pharmacokinetics)
• Rhenium (chemistry, pharmacokinetics)
• Technetium (chemistry, pharmacokinetics)
• Tissue Distribution