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

Abstract

The zinc dithiocarbamates functionalized with folic acid 2Zn and 3Zn were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (1Zn). Zinc complexes 2Zn and 3Zn 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 2Zn or 3Zn and the cation fac-[99mTc(H2O)3(CO)3]+, in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac-[99mTc(CO)3(SS)(P)] bioconjugated to folic acid (2Tc and 3Tc). In spite of the low solubility of 2Zn and 3Zn 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 (2Re and 3Re) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2Tc and 3Tc indicate low specific binding to folate receptors. In summary, Tc-99m folates 2Tc and 3Tc 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.

Synthesis, characterization and in vitro cytotoxicity of gallium(iii)-dithiocarbamate complexes

“…33,[36][37][38][39] In addition, DTC complexes have been used efficiently in the radiopharmaceuticals field, for the development of homoleptic and heteroleptic technetium and rhenium complexes for SPECT imaging and radiation therapy. [40][41][42][43][44][45][46][47][48][49][50][51] The DTC affinity for gallium has been well established since 1974. With gallium(III) they usually form stable mononuclear homoleptic complexes of the type [Ga(DTC) 3 ], characterized by a GaS 6 core with a trigonal prismatic or triple-helix symmetry rather than an octahedral one, due to the small bite angle of the CS 2 group, though heteroleptic complexes have also been described.…”

“…33,36–39 In addition, DTC complexes have been used efficiently in the radiopharmaceuticals field, for the development of homoleptic and heteroleptic technetium and rhenium complexes for SPECT imaging and radiation therapy. 40–51…”