DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is a very effective chelator for many metal ions. The Gd complex is used as an MRI contrast agent and bifinctional DOTA derivatives are frequvently used to construct targeted radiopharmaceuticals.
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. DOTA is a very effective chelator for many metal ions including calcium, strontium, copper, zinc, manganese, yttrium, gadolinium, europium, terbium, lutetium, samarium, thulium, actinium. The molecule is synthesized by alkylating cyclen with chloroacetic acid or bromoacetic acid. The ligand forms especially stable complexes with lanthanides, which have exceptionally high thermodynamic stability and kinetic inertness. NMR studies of the lanthanide complexes (Ln = La, Pr, Nd, Sm, Eu, Yb, Tb, Ho, Dy, Er, Tm, Lu) have revealed that in aqueous solutions the structure of the major isomer of the lighter lanthanides corresponds to that of the minor isomer of the heavier lanthanides. The gadolinium complex of dota is used as a magnetic resonance imaging (MRI) contrast agent. The minor isomer has faster water exchange rate and thus the corresponding gadolinium complex has higher water relaxivity. DOTA is the most advantageous chelator for radioimmunotherapy with yttrium-90 and radioactive lanthanide isotopes. DOTA can hold yttrium with very high kinetic stability in vivo and it was shown to be superior to DTPA, which was reported to release radioactive metal in vivo. DOTA-tris(tert-butyl ester) is frequently used to attach a DOTA unit to peptides using solid phase peptide synthesis.