We investigated the bio-distributions of [125 I]Spiro-I formulated in sterically stabilized liposomes （SSL） or targeted liposomes （SSTL） in mice,especially their brain uptake.The [125 I]Spiro-I liposomes were prepared by film-ultrasound dispersion method.Cereport （RMP-7） was covalently conjugated with DSPE-PEG,which was attached to the surface of SSL to form SSTL.The encapsulation efficiencies （ee%） of [125 I]Spiro-I-SSL and [125 I]Spiro-I-SSTL were 97.47%±4.01% and 93.02%±2.98%,respectively.The average particle sizes were （66.47±0.76） nm and （71.40±0.45） nm,respectively.After intravenous administration,[125 I]Spiro-I was quickly eliminated from blood.SSL could prolong the retention time of [125 I]Spiro-I in blood and SSTL improved its brain uptake.The AUC of [125 I]Spiro-I-SSTL in brain was increased by 1.52 times as compared to [125 I]Spiro-I,indicating that SSTL could be used for the formulation of [125 I]Spiro-I for the imaging of central nervous system （CNS）.
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
