Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl ^99mTc complexes as potent σ₁ receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)-propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)-butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for σ₁ receptors and moderate to high selectivity for σ₂ receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding ^99mTc derivatives [^99mTc] 23 and [^99mTc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [^99mTc]23 or [^99mTc]24 in the brain. Studies of the cellular uptake of [^99mTc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-otolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [^99mTc]23 to σ₁ receptors in the tumor.