Tc-99m radiopharmaceuticals based on a ternary ligand system comprised of a water soluble phosphine

A series of Tc-99m-labeled, hydrazinonicotinamide (Hynic) functionalized bi ologically active molecules (BAMs) have been synthesized using different co mbinations of tricine and. water soluble phosphine (L) as ancillary ligands . One of these, DMP444, Tc-99m-(cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-hydraz inonicotinylamido)hexanamide)))(tricine)(TPPTS) is currently in clinical tr ials as a thrombus imaging agent. The ternary ligand complex of a chemotact ic peptide conjugate, Tc-99m-(fMLFKHynic)(tricine)(TPPTS) has been found to image infection in a rabbit model. The syntheses were performed in one ste p in high yield and high specific activity (similar to 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 rad iopharmaceuticals include: the ability to form the complexes in high yield using low concentrations of the Hynic functionalized BAMs; stability both i n vitro and in vivo; and the ability to tailor the lipophilicity and charge of the complexes by the choice of the water soluble phosphine.