Backbone-substituted DTPA ligands for 90Y radioimmunotherapy.
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.
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
M W
MW
Brechbiel
O A
OA
Gansow
D007167:Immunotherapy; D008024:Ligands; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D011878:Radiotherapy; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D008024:Ligands; D015021:Yttrium Radioisotopes; D004369:Pentetic Acid