Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent

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) ( ^99m Tc]-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 competition binding assays show moderate affinity of Re-2 towards σ₁ and σ₂ receptors with K _i 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. injection indicate the accumulation of ^99m Tc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of ^99m Tc]-2 has been inhibited at 20 h after co-injection of ^99m Tc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of ^99m Tc]-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 ^99m Tc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. ^99m Tc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.