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. 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 60 minutes (tmax). Cumulative residence of 99mTc‐EMIHPBP in the bone [AUC (0−∞) (%ID∙min/gram bone)] was 3685.23, mean residence time was 384.354 minutes, 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 263.914 minutes. Excellent bone uptake can be obtained 1‐hour postinjection 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.

A novel zoledronic acid (ZL) derivative, 3‐(2‐ethyl‐4‐methyi‐1H‐imidazole‐1‐yl)‐1‐hydroxy‐1‐phosphonopropyl phosphonic acid (EMI...

Source: Journal of Labelled Compounds and Radiopharmaceuticals - August 24, 2017 Category: Biochemistry Authors: H.A. Motaleb, Ismail Taha Ibrahim, M. El ‐Tawoosy, M.I. Mohamed Tags: RESEARCH ARTICLE Source Type: research