DOTAderivaten

DOTAderivate, or DOTA derivatives, are chemical compounds based on DOTA, the macrocyclic tetraazacyclododecane tetraacetic acid. These ligands are designed to form stable complexes with metal ions and to be conjugated to biomolecules for diagnostic or therapeutic uses. DOTA itself is valued for its high thermodynamic stability and kinetic inertness with a range of trivalent metal ions, including gadolinium, gallium, lutetium, and yttrium.

Chemistry: DOTA has a 12-membered macrocycle with four nitrogen atoms and four pendant acetate arms. Derivatives are created by modifying the pendant carboxylates or by substituting one or more nitrogens, enabling conjugation to peptides, proteins, or other targeting vectors. Such modifications tune charge, hydrophilicity, and the coordination chemistry for specific metals. Many DOTA derivatives are activated with an isothiocyanate or NHS ester for bioconjugation.

Applications: The most prominent use of DOTA derivatives is in radiopharmaceuticals and molecular imaging. DOTA derivatives complexed with gallium-68 or lutetium-177 are used in peptide receptor-targeted imaging and therapy, notably DOTATATE, DOTATOC, and DOTANOC for neuroendocrine tumors. DOTA-Gd complexes, such as gadoteric acid, are employed as MRI contrast agents. DOTA derivatives can also serve as chelators for other radiometals and in targeted radiotherapy or theranostics.

Synthesis and conjugation: Common routes include forming the DOTA chelator, then attaching a biomolecule through a suitable linker or using prefunctionalized amino-acid derivatives, followed by metal complexation.