p-Isothiocyanatobenzyl DTPA is the most commonly used acyclic bifunctional chelator for labeling proteins and other biomolecules for radiopharmaceutical or MRI applications.
p-Isothiocyanatobenzyl DTPA is the most commonly used acyclic 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 DTPA is prepared from p-nitrophenyl alanine in a multistep synthesis. The ligand forms complexes with bismuth, indium, yttrium and lanthanide ions with reasonable thermodynamic stability. These complexes, however, lack the improved kinetic stability of the more rigid DOTA analogs. Despite of the unsatisfactory kinetic stability of its complexes, p-isothiocianatobenzyl DTPA continues to be a very popular bifunctional, partly because it forms complexes significantly faster than DOTA based bifunctionals. P-SCN-benzyl DTPA derivatives with alkyl substituents such as methyl (mx-DTPA) or cyclohexyl (CHX-DTPA) form complexes with improved kinetic stability due to the rigidifying effect of the backbone substitution. Antibodies that have been labeled with p-SCN-benzyl-DTPA include B72.3 ( against metastatic colon cancer), monoclonal antimyosin Fab (AM-Fab), NP-4 (against anti-carcinoembryonic antigen), murine monoclonal antibody (MAb 19-24), KC-4G3 (against human milk fat globule antigen) CO17-1A (against SW 948 human colorectal carcinoma), MA5 and B-B4, (against the epithelial antigens Muc-1 and syndecan-1). Mx-DTPA was used to label a high-affinity IgG1 murine monoclonal anti-CD20 antibody (IDEC-2B8) for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. The yttrium-90 labeled immunoconjugate (Y90-Zevalin) is the first metalloradiopharaceutical approved by the FDA for therapy.