Anti-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid single-chain variable fragment C825 (Anti-DOTA scFv C825)

Anti-DOTA scFv C825 is a high-affinity single-chain variable fragment engineered to bind the metal-chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) with picomolar affinity. It was derived through affinity maturation of the 2D12.5 antibody and is specifically optimized to recognize DOTA complexed with various trivalent radiometals such as Lutetium-177, Yttrium-90, and Actinium-225. In clinical and preclinical settings, C825 is a critical component of pre-targeted radioimmunotherapy (PRIT) platforms, such as the Self-Assembling Disassembling Antibody (SADA) technology. By decoupling the slow-circulating tumor-targeting antibody from the fast-clearing radioactive payload, C825 allows for high radiation doses to be delivered to tumor tissues while minimizing exposure to healthy organs like the bone marrow. This approach addresses the primary limitation of conventional radioimmunotherapy, which is the dose-limiting toxicity caused by the long blood half-life of directly labeled antibodies.

Other names

C825 scFvAnti-DOTA C825scFv C825Anti-metal-DOTA scFv

The C825 scFv acts as a capture reagent in pre-targeted radioimmunotherapy (PRIT). It is typically fused to a tumor-targeting moiety (like an anti-GD2 or anti-GPA33 antibody) to form a bispecific or multivalent construct. This construct is administered first to localize at the tumor site; subsequently, a small-molecule radiolabeled DOTA chelate is administered, which is rapidly captured by the C825 scFv at the tumor while unbound radioligand is quickly cleared from the blood, thereby increasing the therapeutic index.