Tc-99m Radiopharmaceuticals Based on a Ternary Ligand System Comprised of a Water Soluble Phosphine

Abstract

A series of Tc-99m-labeled, hydrazinonicotinamide (Hynic) functionalized biologically active molecules (BAMs) have been synthesized using different combinations of tricine and a water soluble phosphine (L) as ancillary ligands. One of these, DMP444, Tc-99m-(cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-hydrazinonicotinylamido)hexanamide)))(tricine) (TPPTS) is currently in clinical trials as a thrombus imaging agent. The ternary ligand complex of a chemotactic peptide conjugate, Tc-99m-(fMLFKHynic)(tricine)(TPPTS) has been found to image infection in a rabbit model. The syntheses were performed in one step in high yield and high specific activity (∼20,000 Ci/mmol) and the complexes were shown to be stable for > 6 h in the reaction mixture and upon dilution. The advantages of this ternary ligand system for Tc-99m radiopharmaceuticals include: the ability to form the complexes in high yield using low concentrations of the Hynic functionalized BAMs; stability both in vitro and in vivo; and the ability to tailor the lipophilicity and charge of the complexes by the choice of the water soluble phosphine.

Keywords::

• Tc-99m radiopharmaceuticals
• peptides
• water soluble phosphines