1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-metal complex (DOTA-hapten)

The DOTA-hapten complex recognized by C825 is a synthetic small-molecule ligand used in pretargeted radioimmunotherapy (PRIT). It consists of the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexed with a radiometal, such as Lutetium-177, Yttrium-90, or Actinium-225 (Cheal et al., 2014; Cheal et al., 2020). The C825 antibody is a humanized single-chain variable fragment (scFv) with picomolar affinity for these metal-DOTA complexes, specifically the p-aminobenzyl-DOTA (DOTA-Bn) derivative (Orcutt et al., 2011). In clinical applications, a bispecific antibody is first administered to bind a tumor-associated antigen (e.g., GPA33, GD2, or HER2) and provide a localized capture site. After the antibody has cleared from the blood, the radiolabeled DOTA-hapten is injected, allowing it to be rapidly captured by the tumor-bound antibody or quickly excreted via the kidneys (Cheal et al., 2016). This strategy significantly enhances the therapeutic index of radioimmunotherapy by minimizing the exposure of healthy tissues to radiation while maximizing the dose delivered to the tumor.

Other names

DOTA-chelateDOTA-BnM-DOTA-BnRadiohaptenBenzyl-DOTA complexProteus-DOTA

Pretargeted radioimmunotherapy (PRIT) involving the capture of a radiolabeled DOTA-chelate by a tumor-localized bispecific antibody.