Bis-arene complexes of technetium represent a fundamental class of organometallic compounds. Detailed insights into their properties are obtained due to novel and convenient synthetic routes.

The synthesis of piano-stool type complexes [(Cp-R)99mTc(CO)3] from water and, if possible, directly from [99mTcO4]- is a persisting challenge. Such complexes are very convenient for labeling biomolecules since they are small in size and “innocent” with respect to noncovalent interactions in biological systems. We found that [(Cp-R)99mTc(CO)3] can be prepared directly from the dimerized Diels−Alder precursors and from [99mTcO4]-. Since the concentration of the respective monomers in the reaction solutions was undetectable, the formation of [(Cp-R)99mTc(CO)3] must be based on a metal-mediated retro Diels−Alder reaction with concerted Cp coordination. The authenticity of the formed 99mTc complexes was confirmed by comparing their HPLC retention times with those of the structurally characterized rhenium surrogates. Besides the principle access to piano-stool complexes for radiopharmaceutical studies, a metal-mediated retro Diels−Alder reaction under concomitant formation of the corresponding piano-stool complex has, to our knowledge, not been observed before and might apply to other metal cations as well.

Enhanced receptor selectivity: carbonic anhydrase inhibitors are relevant for both cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive (99m)Tc homologs enables the use of identical molecules for therapy and imaging (theragnostic). The syntheses and in vitro evaluation of [(Cp-R)M(CO)(3)] (Cp=cyclopentadienyl, M=Re, (99m)Tc) with R being a highly potent carbonic-anhydrase-targeting vector is reported.

We have synthesized amino acids conjugated at the alpha-carbon through an alkyl spacer to a small tripod ligand. The tripod coordinates to the fac-[M(CO)3]+ moiety (M = Re, 99mTc). Depending on the lengths of the spacers, these metal complexes with pendent alpha-amino acids are recognized and transported by the l-type amino acid transporter LAT1. The best result was achieved with a butyl spacer. The Ki value of the corresponding complex is comparable to that of the artificial amino acid BCH. Efflux of [3H]-l-phenylalanine shows that the labeled amino acids do not only bind to the transporter but are transported into the cells. These are the first metal-labeled small molecules which are actively internalized to the intracellular space.