Synthesis of 99mTc-oxybutynin for M3-receptor-mediated imaging of urinary bladder

Abstract

Radiolabeling of oxybutynin, a muscarinic acetylcholine (mACh) receptor antagonist agent with 99mTc is of considerable interest for imaging of urinary bladder. This study is aimed to optimize radiolabeling yield of oxybutynin with 99mTc using SnCl2·2H2O as a reducing agent with respect to factors that affect the reaction conditions such as oxybutynin amount, stannous chloride amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 8 h. 99mTc-oxybutynin was injected via subcutaneous and intravenous administration routes into normal Sprague–Dawley rats. Biodistribution studies have revealed that 99mTc-oxybutynin exhibits high affinity and specificity for the muscarinic M3 subtype located on the smooth muscle of urinary bladder relative to the M1 and M2 subtypes of the G protein coupled receptor (GPCR) superfamily. In vivo uptake of subcutaneous 99mTc-oxybutynin in urinary bladder was 19.6 ± 0.42% ID at 0.5 h, whereas in intravenous administration route the accumulation in the urinary bladder was found to be 9.4 ± 0.31% ID at 0.5 h post injection. Administration of cold oxybutynin effectively blocked urinary bladder uptake and further confirms the high specificity of this complex for the M3 receptor.