Synthesis and biological evaluation of a novel 99mTc complex of HYNIC-conjugated aminomethylenediphosphonate as a potential bone imaging agent

A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with aminomethylenediphosphonic acid (AMDP) was synthesized through a multiple-step reaction. HYNIC-AMDP could be labeled easily and efficiently with Tc-99m using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) as coligand to form the Tc-99m-HYNIC-AMDP complex in high yield (> 95%). Its partition coefficient indicated that it was a good hydrophilic complex. The biodistribution studies of Tc-99m-HYNIC-AMDP in normal ICR mice showed that this complex had high bone uptake and low or negligible accumulation in non-target organs. As compared with Tc-99m-MDP, Tc-99m-HYNIC-AMDP had a higher bone uptake and the ratios of bone/blood and bone/muscle at early time after injection, suggesting that it could be potentially useful for bone imaging at an earlier time after injection according to further investigations of the biological behavior of this complex.