Water-Soluble [Tc(N)(PNP)] Moiety for Room-Temperature 99m Tc Labeling of Sensitive Target Vectors.

The incorporation of bioactive molecules into a water-soluble [ 99m Tc][Tc(N)(PNP)]-based mixed compound is described. The method, which exploits the chemical properties of the new [ 99m Tc][Tc(N)(PNP3OH)] 2+ synthon [PNP3OH = N , N -bis(di-hydroxymethylenphosphinoethyl)methoxyethylamine], was successfully applied to the labeling of small, medium (cysteine-functionalized biotin and c-RGDfK pentapeptide), and large molecules. Apomyoglobin was chosen as a model protein and derivatized via site-specific enzymatic reaction catalyzed by transglutaminase (TGase) with the H-Cys-Gly-Lys-Gly-OH tetrapeptide for the insertion in the protein sequence of a reactive N-terminal Cys for 99m Tc chelation. Radiosyntheses were performed under physiological conditions at room temperature within 30 min. They were reproducible, highly specific, and quantitative. Heteroleptic complexes are hydrophilic and stable. Biodistributions of the selected compounds show favorable pharmacokinetics within 60 min post-injection and predominant elimination through the renal-urinary pathway. In a wider perspective, these data suggest a role of the [ 99m Tc][Tc(N)(PNP)] technology in the labeling of temperature-sensitive biomolecules, especially targeting proteins for SPECT imaging.