~(99m)Tc-labeled butyl-substituted zoledronic acid as a novel potential SPECT imaging agent: preparation and preclinical pharmacology study

摘要

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, ~(99m)Tc-BIDP [BIDP, 1-hydroxy-2-(2-butyl-1 H-imidazole-1 -yl) ethylidene-1,1 -diphosphonic acid]. It possesses high radiolabeling yield, radiochemical purity, and stability. The biodistribution in mice shows that ~(99m)Tc-BIDP has high specificity in the skeleton with the maximum uptake of 24.6 ± 1.65 % ID g"1 at 120 minpost injection. It can be quickly absorbed and rapidly eliminated from the blood judged from the short distribution half-life (t_(1/2alpha) = 1.65 min) and elimination half-life (t_(1/2beta) = 30.91 min). The bone imaging of the rabbit showed that ~(99m)Tc-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.