Novel ~(99m)Tc labeled σ receptor ligand as a potential tumor imaging agent

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A novel 99mTc 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′-99mTcO) ([99mTc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA′-ReO)(Re-2) has been prepared and characterized. In vitro competi-tion binding assays show moderate affinity of Re-2 towards σ1 and σ2 receptors with Ki values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. in-jection indicate the accumulation of [99mTc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [99mTc]-2 has been inhibited at 20 h after co-injection of [99mTc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [99mTc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [99mTc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [99mTc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors. A novel 99mTc labeled complex, 2-aminoethanethiolato [2- (4- (3-phenylpropyl) piperazin-1-yl) ethyl) The corresponding rhenium complex (PPPE-MAMA’-ReO) (Re-2) has been designed and prepared based on the integrated approach. prepared and characterized. In vitro competi-tion binding assays show affinity affinity of Re-2 towards σ1 and σ2 receptors with Ki values ​​of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images were obtained at 0.5 h, 4 h, 20 h after iv in-jection indicate the accumulation of [99mTc] -2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [99mTc] -2 has been inhibited at 20 h after co-injection of [99mTc ] -2 plus haloperidol (1 mg / kg). Biodistribution studies of [99mTc] -2 display an in vivo tumor uptake of 0.14% ± 0.01% ID / g at 24 h post iv injection with a tumor / muscle ratio of 6.02 ± 0.87. The above results suggest that [99mTc] -2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [99mTc] -2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors .
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