Preparation of new [[Tc-99m](MeOBzEN)(H2O)(CO)(3)](+) complexes and in vitro evaluation as potential tumor diagnostic radiopharmaceutical

Abstract

Objectives: In the present study we sought to prepare and evaluate the uptake of [[99m Tc](MeOBzEN)(H2O)(CO)3] + in breast cancer cells, MDA-MB-231, in suspension or in monolayer and to compare the results with [[99m Tc](MIBI)6] +, and a well-established radiopharmaceutical for breast cancer detection. Methods: The ligand L1: N-(4-methoxybenzil)ethylenediamine and L2: N,N ́-(di-4-methoxybenzil)ethylenediamine was synthesized by reaction between ethylenediamine and 4-methoxybenzaldehyde, followed by NaBH4 reduction. [[99m Tc](L1)(H2O)(CO)3] + and [[99m Tc](L2)(H2O)(CO)3] + (figure 1) were obtained by CO/NaBH4 standard reaction procedure, and quality controls (LogP, electrophoresis, HPLC) were performed. MDA-MB-23 was growth in RPMI-1640 culture media with 10% fetal bovine serum and part was allowed in suspension and other part was adhered in 12-well plates. Technetium radiopharmaceuticals were added to cells in suspension or monolayer and incubated at 37°C. At 10, 30 and 60 minutes, culture medium and cells were separated by centrifugation and activity was measured in a well counter. Figure 1. Structure of [[99m Tc](MeOBzEN)(H2O)(CO)3] + complex and uptake behavior in MDA-MB-231 cell culture (sus = suspension; mon = monolayer) Results: Ligands were obtained in 68% yield and technetium complex with overall yield high of 90% and were stable at least for four hours, LogP values were 0.266 ± 0.075 and 0.718 ± 0.018, for complex L1 and L2, against 1.330 ± 0.127 for MIBI. Complexes charge was inconclusive, once it depends of electrolitic system. Uptakes of both new complexes were high as compared to [[99m Tc](MIBI)6] +, and the value depends if cells are in suspension or adhered, as show in figure 1. Conclusions: The new [[99mTc](MeOBzEN)(H2O)(CO)3]+ were obtained in high yields and uptake in MDA-MD-231 culture cell is higher than [[99m Tc](MIBI)6]+, suggesting a potential use as radiopharmaceutical. However, it's not clear difference between uptake in suspension and adhered cell and further investigation are been undertaken, including animal imaging.