Development of superior bone scintigraphic agent from a series of 99mTc-labeled zoledronic acid derivatives

Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of 99mTc-ZL and 99mTc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent 99mTc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that 99mTc-IPeDP would be a novel superior bone scintigraphic agent.

► Two novel diphosphonic acids were labeled with the 99mTc in high labeling yield. ► 99mTc-IPeDP had high uptake in skeletal system and rapid clearance from blood. ► 99mTc-IPeDP reveals attractive biological features as superior bone scanning agent.