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

Introduction: To 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. Methods: A novel ZL derivative, 1-hydroxy-3-(1H-imidazol-1-yl)propane-1,1-diyldiphosphonic acid (IPrDP), was successfully prepared and labeled with (99m)Tc in a high labeling yield. Biodistribution of (99m)Tc-IPrDP and (99m)Tc-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. Results: In the biodistribution studies, (99m)Tc-IPrDP exhibits significant advantages on the bone resorption and the clearance from soft tissues compared with (99m)Tc-ZL. Kinetics of blood clearance in mice showed that T(1/2 alpha) and T(1/2 beta), of (99m)Tc-IPrDP were 1.47 min and 46.47 min, while those of (99m)Tc-ZL were 2.28 and 52.63 min respectively. Excellent images of the rabbit skeleton can be quickly obtained for (99m)Tc-IPrDP, which was faster than (99m)Tc-ZL and the clinically widely used bone imaging agent (99m)Tc-MDP (technetium-99m labeled with methylenediphosphonate). Conclusions: (99m)Tc-IPrDP possesses excellent characteristics for the potential application as a novel bone scanning agent. (C) 2011 Elsevier Inc. All rights reserved.