Backbone-substituted DTPA ligands for yttrium-90 radioimmunotherapy

Abstract
Four new bifunctional diethylenetriaminepentaacetic acid (DTPA) ligands were synthesized to provide an improved chelating agent for radioimmunotherapy with 90Y. The new DTPA ligands contained a 4-isothiocyanatobenzyl group (pSCNBz) substituted onto the carbon backbone of DTPA for use in linkage to immunoprotein. Methyl groups were strategically incorporated onto the backbone of the ligands via a peptide route to provide 2-pSCNBz-5-Me-DTPA (2) and 3-Me-6-pSCNBz-DTPA (3). Addition of these functionalities was expected to sterically hinder the release of radiometal from the chelate. A new monosubstituted ligand, 3-pSCNBz-DTPA (4), was also prepared in order to determine whether a shift in position of the linking group had an effect on the in vivo stability of the yttrium complex. Additionally, by modification of known methods, a disubstituted DTPA ligand, 2-pSCNBz-6-Me-DTPA (1), was prepared.