Anti-DOTA binding site (Anti-DOTA)

The anti-DOTA binding site is an engineered antibody-derived domain, typically a single-chain variable fragment (scFv) such as the high-affinity C825 fragment, designed to specifically recognize and bind the metal-chelate complex 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (Schaffer et al., 2016, PMID: 26865561). This binding site is a foundational element of pre-targeted radioimmunotherapy (PRIT), a strategy developed to improve the therapeutic index of radiopharmaceuticals in oncology. In this system, a bispecific antibody containing the anti-DOTA site is used to pre-target tumor cells by binding to a specific surface antigen. Once the antibody has cleared from the bloodstream, a small-molecule radioligand consisting of a radionuclide (e.g., Lutetium-177 or Actinium-225) chelated by DOTA is administered. The anti-DOTA binding site captures this radioligand with high affinity and stability, ensuring that the radiation is delivered directly to the tumor site (Orcutt et al., 2012, PMID: 22167171). This approach significantly reduces the radiation dose to healthy organs, particularly the bone marrow, compared to conventional radioimmunotherapy where the radionuclide is directly conjugated to a full-length antibody.

Other names

Anti-DOTA scFvAnti-DOTA FabC825 antibody fragmentDOTA-binding armAnti-metal-DOTA binding siteAnti-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid binding site

The anti-DOTA binding site acts as a molecular anchor in pre-targeted radioimmunotherapy (PRIT). A bispecific antibody is first administered to bind a tumor-associated antigen; once localized and cleared from the blood, a radiolabeled DOTA-chelate is administered and captured by this site at the tumor (Cheal et al., 2016, PMID: 27197067).