A novel ^(99m)Tc labeled complex,[N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl)(2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(Ⅴ) oxide (PPPE-MAMA''-^(99m)TcO)([^(99m)Tc]-2) has been designed and prepared based on the integrated approach. The correspondingrhenium complex (PPPE-MAMA''-ReO)(Re-2) has been prepared and characterized. In vitro competitionbinding assays show moderate affinity of Re-2 towards σ_1 and σ_2 receptors with K_i values of8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h afteri.v. injection indicate the accumulation of [^(99m)Tc]-2 in MCF-7 human breast tumor bearing mice at20 h. Furthermore, the accumulation of [^(99m)Tc]-2 has been inhibited at 20 h after co-injectionof [^(99m)Tc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [^(99m)Tc]-2 display an invivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of6.02 ± 0.87. The above results suggest that [^(99m)Tc]-2, derived from a previously published leadcompound, retains certain tumor uptake and affinity for σ receptors. [^(99m)Tc]-2 may be used as abasis for further structural modifications to develop tumor imaging agents with high affinity for σreceptors.
FAN Caiyun1, JIA Hongmei1, Deuther-Conrad Winnie2, Brust Peter2, Steinbach J?rg2 & LIU Boli1 1. Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China
