Abstract
1129
Objectives To evaluate the behavior of the [99mTc(MIBI)6]+ and new complexes [99mTc(O)2(N-(MeOBz)EN)2]+ and [99mTc(O)2(N,N-(MeOBz)EN)2]+ in the sensitive (MES-SA) and drug resistant (MES-SA/Dx5) cells.
Methods Ligands were synthesized by 4-methoxybenzaldehyde and ethylenediamine reductive amination. 99mTc-complexes were prepared in buffer (pH 9), reacting 10 mg ligands, [99mTcO4]- and 1.25 µg Sn2+. [99mTc(MIBI)6]+ was from in house produced kit. Labeling efficiency and stability, under labeling condition and in presence of cysteine and histidine, at 37oC, were assessed. Complexes charge and LogP were determined by routine procedures. Toxicity of ligands was assessed by MTT method. Cells were incubated with 99mTc-complexes in absence or presence of 10µL of verapamil (VER) (50 µM) at 37oC or at 4oC, for 60 min. After separation, activity in liquid phase and cell were measured, and presented as % uptake.
Results Labeling yield were higher than 90 % and 99mTc-complexes were stable for 24 h, but just for 4 h in presence of the aminoacids. All complexes showed positive charge. Ligands were not toxic at 1000 times used concentration. Uptake of the 99mTc-complex in MES-SA, MES-SA/Dx5 and MES-SA/Dx5 + VER, were: [99mTc(O)2(N-(MeOBz)EN)2]+ (LogP 0.26) = 0.18±0.04, 0.18±0.07 and 0.08±0.04; [99mTc(O)2(N,N-(MeOBz)EN)2]+ (LogP 1.60)= 0.85±0.04, 1.27±0.05 and 0.53±0.03; [99mTc(MIBI)6]+ (LogP 1.33) = 1.72±0.15, 0.53±0.03 and 0.36±0.05. At 4oC uptake is lower than 0.4 for all complex. More than 90 % of the cells remained viable by Tripan blue method.
Conclusions Lipophilic complex [99mTc(O)2(N,N-(MeOBz)EN)2]+ showed high uptake in both tumor cells, but VER decrase its uptake sugesting it can be considered a modulator instead a substract. Concentration of VER was not enough to revert resistance phenomeno for [99mTc(MIBI)6]+ uptake in MES-SA/Dx5 line.
Research Support FAPESP 06/50296-0
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