Complexes with the fac-{M(CO)3}+ (M = 99mTc, Re) moiety and long alkyl chain ligands as Lipiodol surrogates

Accumulation of radiopharmaceuticals in the liver is frequently observed and represents in general a limiting factor when developing novel labeled compounds for any purpose in nuclear medicine. Aiming at the treatment of liver cancer with radiopharmaceuticals, such accumulation is desired but the compounds have to remain in the liver over an extended time period rather than being washed out or redistributed over time in the whole body. Lipiodol is known to remain in the liver and we present here a study for the preparation of 186Re and 99mTc labeled Lipiodol surrogates expected to behave similarly. We have synthesized two bidentate and two tridentate ligands conjugated to a pendant C18 chain as well as their corresponding fac-[Re(CO)3]+ and fac-[Tc(CO)3]+ complexes. Three of the rhenium complexes have been structurally characterized. Labelling with [186Re(OH2)3(CO)3]+ and [99mTc(OH2)3(CO)3]+, respectively, gave yields in the range of 90%. The complexes could be extracted into Lipiodol due to their high lipophilicity and close structural relationship with the major components of Lipiodol. The complexes are stable in water and in Lipiodol for more than 24 h. These Lipiodol surrogates present new low-valent technetium and rhenium complexes for applications in liver cancer imaging and therapy.

Graphical abstractThe synthesis and characterization of new fac-[M(CO)3]+ (M = Tc, Re) based complexes with bi- and tridentate ligands and a pendant C18 chain is described. The synthetic approach can be extended to other, purely aliphatic, or derivatized long-alkyl chains. Due to the lipophilicity of the complexes they are potential surrogates for Lipiodol, a liver cancer therapy agent. The ligands have been labeled with 99mTc and 186Re. The complexes are very stable which makes them suitable for application in radioimaging and –therapy.Figure optionsDownload full-size imageDownload as PowerPoint slide