Preparation and in vivo biological investigations on a novel radioligand for bone scanning: technetium-99m-labeled zoledronic acid derivative

IntroductionTo enable imaging at an earlier time after injection, a radiopharmaceutical with higher affinity for bone, larger ratio of bone-to-soft tissue uptake and more rapid clearance from blood is required. The nature of diphosphonic acid is a key factor to determine the advantages of the radiopharmaceuticals. The purpose of this study is to optimize the linker chain between the imidazolyl and geminal diphosphonate group in the zoledronic acid (ZL) to develop novel single photon emission computed tomography (SPECT) bone imaging agent.MethodsA novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with 99mTc in a high labeling yield. Biodistribution of 99mTc-IPrDP and 99mTc-ZL in normal mice were studied and compared. SPECT bone scanning was performed on the rabbit and a series of dynamic and static images were recorded by Philips SKY Light emission computed tomography.ResultsIn the biodistribution studies, 99mTc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with 99mTc-ZL. Kinetics of blood clearance in mice showed that T1/2α and T1/2β of 99mTc-IPrDP were 1.47 min and 46.47 min, while those of 99mTc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for 99mTc-IPrDP, which was faster than 99mTc-ZL and the clinically widely used bone imaging agent 99mTc-MDP (technetium-99m labeled with methylenediphosphonate).Conclusions99mTc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent.