Anti-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid single-chain variable fragment (Anti-DOTA scFv) (anti-DOTA scFv)

The anti-DOTA single-chain variable fragment (scFv) is an engineered protein component used in bispecific antibody platforms to facilitate pre-targeted radioimmunotherapy (PRIT) and diagnostic imaging. It is designed to bind with picomolar affinity to DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexes, which are common chelating agents for medical radionuclides like Lutetium-177, Yttrium-90, and Actinium-225. In a therapeutic setting, a bispecific antibody containing this scFv is first used to target a specific tumor antigen (such as GPA33 or GD2). After the antibody has cleared from systemic circulation, a small-molecule radiolabeled DOTA-hapten is administered, which rapidly binds to the anti-DOTA scFv localized at the tumor site. This method allows for high radiation doses to be delivered to the tumor while sparing healthy tissues from the prolonged circulation of radiolabeled antibodies. The most well-characterized version of this scFv is the C825 clone, which has been optimized for stability and ultra-high affinity to various metal-DOTA complexes (Cheal et al., 2017, Journal of Nuclear Medicine; Zhou et al., 2021, Frontiers in Oncology).

Other names

C825 scFvanti-DOTA antibody fragmentDOTA-binding scFvanti-chelate scFv

The anti-DOTA scFv acts as a high-affinity docking site in pre-targeted radioimmunotherapy (PRIT). A bispecific antibody (bsAb) is administered first to localize to tumor antigens; once blood levels of the bsAb decline, a radiolabeled DOTA-chelate (hapten) is injected, which is captured by the anti-DOTA scFv at the tumor site (Cheal et al., 2016, Blood; Orcutt et al., 2012, Molecular Cancer Therapeutics).