New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives.

The zinc dithiocarbamates functionalized with folic acid and were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (). Zinc complexes and show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes or and the cation -[Tc(HO)(CO)], in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes -[Tc(CO)(SS)(P)] bioconjugated to folic acid ( and ). In spite of the low solubility of and in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes ( and ) previously synthesized and characterized by standard methods. Preliminary in vivo studies with and indicate low specific binding to folate receptors. In summary, Tc-99m folates and were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step.