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

A novel zoledronic acid (ZL) derivative, 3‐(2‐ethyl‐4‐methyi‐1H‐imidazole‐1‐yl)‐1‐hydroxy‐1‐phosphonopropyl phosphonic acid (EMIHPBP), was synthesized, characterized and successfully radiolabeled with 99mTc. The in‐vivo biodistribution of 99mTc‐EMIHPBP was investigated and compared with the previously reported zoledronate derivatives aiming to formulate a novel zoledronate derivative with a high potential uptake to bone as a promising antiosteoporotic candidate. In order to further evaluate the bone uptake efficiency, the pharmacokinetics of 99mTc‐EMIHPBP was investigated, and showed that maximum concentration in bone (Cmax) was 31.60±0.15%ID/gram after 60min (tmax). Cumulative residence of 99mTc‐EMIHPBP in the bone [AUC (0‐∞) (%ID.min /gram bone)] was 3685.23, mean residence time (MRT) was 384.354min and the calculated bone bioavailability was 15.831%. Finally, the time needed for half of the 99mTc‐EMIHPBP formulation to be eliminated from bone (t1/2) was 263.914min. Excellent bone uptake can be obtained 1h post injection with high bone\blood ratio of 23.76 detected with gamma counter. The biodistribution and kinetic studies could recommend EMIHPBP as a promising antiosteoporotic candidate with high selectivity to the skeletal system and rapid clearance from soft tissues.

Source: Journal of Labelled Compounds and Radiopharmaceuticals - June 15, 2017 Category: Biochemistry Authors: H.A. Motaleb, I.T. Ibrahim, M. El ‐Tawoosy, M.I. Mohamed Tags: RESEARCH ARTICLE Source Type: research