99mTc-labeled butyl-substituted zoledronic acid as a novel potential SPECT imaging agent: preparation and preclinical pharmacology study

Zoledronic acid (ZL) is the most potent among the tested diphosphonates. To develop a superior bone imaging agent that could improve the efficiency of bone scanning, an optimized radiotracer was designed from ZL and prepared successfully, 99mTc-BIDP [BIDP, 1-hydroxy-2-(2-butyl-1H-imidazole-1-yl) ethylidene-1,1-diphosphonic acid]. It possesses high radiolabeling yield, radiochemical purity, and stability. The biodistribution in mice shows that 99mTc-BIDP has high specificity in the skeleton with the maximum uptake of 24.6 ± 1.65 % ID g−1 at 120 min post injection. It can be quickly absorbed and rapidly eliminated from the blood judged from the short distribution half-life (t1/2α = 1.65 min) and elimination half-life (t1/2β = 30.91 min). The bone imaging of the rabbit showed that 99mTc-BIDP has highly selective uptake in the skeletal system and rapid clearance from the soft tissues. An excellent scintigraphic image can be obtained at 1 h with clear visualization of the skeleton.