p-Isothiocyanatobenzyl-DOTA is the most commonly used cyclic bifunctional chelator for labeling proteins and other biomolecules for radiopharmaceutical or MRI applications.
p-Isothiocyanatobenzyl-DOTA is the most commonly used cyclic bifunctional chelator for labeling proteins and other biomolecules for radiopharmaceutical or MRI applications. The SCN groups react very efficiently and selectively with primary amino groups. P-SCN-benzyl DOTA is prepared from p-nitrophenyl alanine in a multistep synthesis. The ligand forms complexes with many metal ions including bismuth, copper, indium, gallium, yttrium, lanthanides and actinides with exceptionally high thermodynamic and kinetic stability. Complexes of the macrocyclic DOTA-based ligands show enhanced thermodynamic and kinetic stability as compared to an open-chain analogue such as EDTA or DTPA. The increase in the thermodynamic stability, known as the macrocyclic effect, is due to the enthalpic and entropic contributions resulting from the preorganization of the macrocyclic framework. One disadvantage of p-SCN-benzyl DOTA is its slow complex formation. p-Isothiocyanatobenzyl DOTA has successfully been used to attach yttrium-90, bismuth-212/213, lutetium-177, indium-111, and actinium-225 to various antibodies including HuM195 (anti-CD33, specific for leukemia cells) B4 (anti-CD19, specific for Daudi and Ramos lymphoma cells), herceptin (anti- HER2/neu specific for MCF7breast carcinoma and SKOV3 ovarian cancer cells), J591 (anti-PSMA, specific for LNCaP.FGC prostate carcinoma cells).