A novel approach to the high-specific-activity labeling of small peptides with the technetium-99m fragment [Tc-99m(N) (PXP)](2+) (PXP = diphosphine ligand)

A new labeling approach for incorporating bioactive peptides into a technet ium-99m coordination complex is described. This method exploits the chemica l properties of the novel metal-nitrido fragment [Tc-99m(N)(PXP)](2+), comp osed of a terminal Tc equivalent toN multiple bond bound to an ancillary di phosphine ligand (PXP). It will be shown that this basic, molecular buildin g block easily forms in solution as the dichloride derivative [Tc-99m(N)(PX P)Cl-2], and that this latter complex selectively reacts with monoanionic a nd dianionic, bidentate ligands (YZ) having soft, pi -donor coordinating at oms to afford asymmetrical nitrido heterocomplexes of the type [Tc-99m(N)(P XP)(YZ)](0/+) without removal of the basic motif [Tc-99m(N)(PXP)](2+). The reactions of the amino acid cysteine was studied in detail. It was found th at cysteine readily coordinates to the metal fragment [Tc-99m(N)(PXP)](2+) either through the [NH2, S-] pair of donor atoms or, alternatively, through the [O-, S-] pair, to yield the corresponding asymmetrical complexes in ve ry high specific activity. Thus, these results were conveniently employed t o devise a new, efficient procedure for labeling short peptide sequences ha ving a terminal cysteine group available for coordination to the [Tc-99m(N) (PXP)](2+) fragment. Examples of the application of this novel approach to the labeling of the short peptide ligand H-Ar g-Gly-Asp-Cys-OH (H(2)1) and of the peptidomimetic derivative H-Cys-Val-2-Nal-Met-OH (H2) will be discus sed.