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.

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

“…including N−O, 12,13 O-O, 14 P-P 15 and Se-Se chelates, [16][17][18][19][20] N,N,N-tridentate chelates [21][22][23][24][25][26] or bridged di-or tri-nuclear alkoxo/hydroxo are also known. [27][28][29] Additionally, but rarer, phototoxic Re complexes capable of either generating reactive oxygen species (ROS) or liberating CO have also been identified.…”

Synthesis and Substitution Kinetics of Tricarbonylrhenium(I) Dendritic Complexes

“…However, exploratory chemical synthesis of technetium‐99m complexes in developmental chemistry is limited by the lack of nonradioactive isotopes of Tc. Thus, complexes of nonradioactive rhenium, which is a technetium congener, are often used as 99m Tc models …”

“…Rhenium and technetium have similar ionic radii, and their fac ‐[M(CO) 3 X] + (where M = 99m Tc I or Re I ; X = halide) containing complexes are often isostructural and relatively similar in chemical reactivity (although they require different reaction conditions) , . It is also possible to use β‐emitting rhenium isotopes ( 186 Re and 188 Re) for radiotherapy applications .…”

“…It is also possible to use β‐emitting rhenium isotopes ( 186 Re and 188 Re) for radiotherapy applications . The low‐spin d 6 fac ‐[M(CO) 3 ] + (where M = Mn I , 99m Tc I , and Re I ) fragment is lipophilic in nature, chemically robust compared to pure organic molecules, and maintains its structural integrity under harsh conditions . In addition to its kinetic stability, its kinetic behavior is an aspect worth considering, as it can influence the uptake and clearance of radiopharmaceutical agents.…”

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

“…In addition, the tricarbonyl technetium-99m ( 99m Tc-(CO) 3 ) unit has been shown to be useful for introducing 99m Tc into biomolecules because of its high chemical stability and small size. In order to take advantage of molecular imaging techniques with 99m Tc-(CO) 3 , many low-molecular weight 99m Tc(I)-complex with tridentate ligands have been developed and used for the preparation of 99m Tc-(CO) 3 -labeled radiotracers [19,20,21,22,23,24]. …”