A solid phase-assisted approach for the facile synthesis of a highly water-soluble zirconium-89 chelator for radiopharmaceutical development. Issue 47 (13th November 2017) - Briand, Manon
Abstract : The solid-phase synthesis of a water-soluble bifunctional chelator for 89 Zr is reported. Abstract : Nuclear medicine has seen impressive growth in recent years. An important development in this field occurred through the application of new radionuclides, e.g., 89 Zr ( t 1/2 = 78.4 h, β + 0.396 MeV), the physical properties of which allow the use of antibodies as biological vectors for specific cancer targeting in combination with high resolution imaging by positron emission tomography (PET). The most commonly used chelator for 89 Zr-based PET imaging is the hexadentate desferrioxamine (DFO) chelator. However, due to the instability of this complex, there has been a strong push towards the development of octadentate chelators. We report an ether derivative, oxoDFO*, resembling the motif of DFO with four hydroxamic acid groups for the binding of the radiometal and four ether linkages to increase the water solubility. Very importantly, the synthesis of this chelator follows a solid phase-assisted approach allowing for the development of an attractive synthetic methodology and widening the scope for the access to DFO-like chelators in highly efficient synthetic sequences.