Preparation of a lysine-based DTPA derivative for the conjugation with biomolecules

For radiopharmaceutical development, many bifunctional chelating agents (BFCAs) have been synthesized and applied. Among them, EDTA(Ethylenediamine tetra-acetic acid) and DTPA(Diethylenetriamine penta-acetic acid) have been used for the radiolabeling with lanthanide nuclides. Until now, many of researches are applying the cyclic DTPA dianhydride to introduce DTPA chelator to bioactive molecules. However, its inherent disadvantage is that DTPA dianhydride produces major side product DTPA bis-molecules, which may cause instability of radionuclide binding in-vivo. In this study, in order to develop the DTPA based bifunctional chelator for the radiolabeling with radionuclides including Re-188, In-111, Y-90, Ho-166, Lu-177 and so on, we prepare lysine-based DTPA derivative. We describe, herein, the convenient synthetic method of the lysine based DTPA derivative derived from Nε - Z protected lysine