| Summary: | The zinc dithiocarbamates functionalized with folic acid <b>2<sub>Zn</sub></b> and <b>3<sub>Zn</sub></b> were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (<b>1<sub>Zn</sub></b>). Zinc complexes <b>2<sub>Zn</sub></b> and <b>3<sub>Zn</sub></b> 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 <b>2<sub>Zn</sub></b> or <b>3<sub>Zn</sub></b> and the cation <i>fac</i>-[<sup>99m</sup>Tc(H<sub>2</sub>O)<sub>3</sub>(CO)<sub>3</sub>]<sup>+</sup>, in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes <i>fac</i>-[<sup>99m</sup>Tc(CO)<sub>3</sub>(SS)(P)] bioconjugated to folic acid (<b>2<sub>Tc</sub></b> and <b>3<sub>Tc</sub></b>). In spite of the low solubility of <b>2<sub>Zn</sub></b> and <b>3<sub>Zn</sub></b> 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 (<b>2<sub>Re</sub></b> and <b>3<sub>Re</sub></b>) previously synthesized and characterized by standard methods. Preliminary in vivo studies with <b>2<sub>Tc</sub></b> and <b>3<sub>Tc</sub></b> indicate low specific binding to folate receptors. In summary, Tc-99m folates <b>2<sub>Tc</sub></b> and <b>3<sub>Tc</sub></b> 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.
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