Synthesis and pharmacological evaluation of ^99mTc‐labeled imidazolyl‐containing diphosphonic acid as a novel bone imaging agent

Abstract

In order to develop a superior bone imaging agent, a new radiotracer (99m)Tc-1-hydroxy-5-(2-butyl-1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (BIPeDP) was designed and prepared with good radiochemical yield and stability. The biodistribution in mice shows that (99m)Tc-BIPeDP has high specificity in the skeleton with the maximum uptake of 17.30 ± 0.14 injected dose per gram at 60 min. Kinetics of blood clearance shows that the distribution half-life (T1/2α) and elimination half-life (T1/2β) of (99m)Tc-BIPeDP are 3.7 and 49.7 min, respectively. An excellent image can be obtained at 1-h post-injection with the single photon emission computed tomography bone scanning, which is clearer and quicker than (99m)Tc-zoledronic acid, (99m)Tc-1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid, and (99m)Tc-methylenediphosphonic acid All results indicate that (99m)Tc-BIPeDP holds great potential as a novel promising bone imaging agent.

Synthesis, preclinical, and pharmacokinetic evaluation of a new zoledronate derivative as a promising antiosteoporotic candidate using radiolabeling technique

“…At 60‐min pi, the bone uptake was 31.60 ± 0.15%ID/g. Comparing these results with radiolabeled ZL or other ZL derivatives, such that 99m Tc‐MIPrDP have maximum bone uptake of 19.6%IDC at 120 minutes and 99m Tc‐BIDP with the maximum uptake of 24.6 ± 1.65% ID/g at 120 min pi . These results could be illustrated by the fact that the bone uptake increases with the increasing carbon chain between the imidazolyl and geminal bisphosphonate group in ZL (ie, from 99mTc‐ZL and 99mTc‐IPrDP to 99m Tc‐EMIHPBP).…”

“…Comparing these results with radiolabeled ZL or other ZL derivatives, such that 99m Tc-MIPrDP have maximum bone uptake of 19.6%IDC at 120 minutes and 99m Tc-BIDP with the maximum uptake of 24.6 ± 1.65% ID/g at 120 min pi. 31 These results could be illustrated by the fact that the bone uptake increases with the increasing carbon chain between the imidazolyl and geminal bisphosphonate group in ZL (ie, from 99mTc-ZL and 99mTc-IPrDP to 99m Tc-EMIHPBP). This implied that the bone uptake efficiency of the former with a methyl in the imidazole ring is larger than the latter with no substituent in the imidazole ring.…”