A novel 99mTc-labeled dimethyl-substituted zoledronic acid (DMIDP) with improved bone imaging efficiency

A novel zoledronic acid (ZL) derivative, 1-hydroxy-2-(2,4-dimethyl-1H-imidazol-1-yl)-ethane-1,1-diyldiphosphonic acid (DMIDP, dimezoledronate), was successfully prepared and labeled with 99mTc in a high labeling yield. The biodistribution in mice shows that 99mTc-DMIDP has significant advantage regarding bone resorption and clearance from soft tissues compared with 99mTc-ZL and the clinically widely-used bone-imaging agent 99mTc-MDP (methylenediphosphonic acid). Kinetics of blood clearance displayed that distribution half-life (T1/2α) and elimination half-life (T1/2β) of 99mTc-DMIDP were 2.53 min and 23.53 min, while those of 99mTc-ZL were 2.28 and 52.63 min, respectively. Excellent images of the rabbit skeleton can be quickly obtained from 99mTc-DMIDP, which was faster than 99mTc-ZL and 99mTc-MDP. The present findings indicate that 99mTc-DMIDP possesses excellent potential for application as a novel bone scanning agent. (orig.)