Amino Acids Labeled with [^99mTc(CO)₃]⁺ and Recognized by the l-type Amino Acid Transporter LAT1

We have synthesized amino acids conjugated at the α-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 α-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.