A novel bifunctional chelating agent based on bis(hydroxamamide) for 99mTc labeling of polypeptides

This paper describes the synthesis and biological evaluation of a novel bifunctional chelating agent (BCA) based on bis (hydroxamamide) for 99m Tc labeling of polypeptides. We successfully designed and synthesized C 3 (BHam) 2 ―COOH as a new BCA. C 3 (BHam) 2 ―COOH formed a stable 99m Tc complex and enabled us to prepare 99m Tc‐labeled polypeptides by using a 2,3,5,6‐tetrafluorophenol (TFP) active ester of C 3 (BHam) 2 ―COOH. 99m Tc‐C 3 (BHam) 2 ―HSA prepared with C 3 (BHam) 2 ―TFP was stable in both murine plasma and an excess of l ‐cysteine without any dissociation of 99m Tc from polypeptides. Furthermore, the blood clearance of 99m Tc‐C 3 (BHam) 2 ―HSA in mice was similar to that of 125 I‐HSA, suggesting that C 3 (BHam) 2 ―COOH retained stable binding between 99m Tc and the polypeptides in vivo . When 99m Tc‐C 3 (BHam) 2 ―NGA was injected into mice, the radioactivity showed high hepatic uptake early on and a rapid clearance from the liver, indicating that C 3 (BHam) 2 ―COOH did not affect the pharmacokinetics of polypeptides in vivo and gave radiometabolites, which displayed a rapid elimination from the liver. Such characteristics would render C 3 (BHam) 2 ―COOH attractive as a new BCA for 99m Tc labeling of polypeptides.