lutetium Lu 177-DTPA-omburtamab

A radioimmunoconjugate consisting of omburtamab, a murine immunoglobulin G1 (IgG1) antibody directed against the surface immunomodulatory glycoprotein human B7-homolog 3 (B7-H3, CD276), conjugated, via the chelating agent diethylenetriaminepentaacetic acid (DTPA), to the radioisotope lutetium Lu 177, with potential antineoplastic activity. Upon intracerebroventricular administration of lutetium Lu 177-DTPA-omburtamab, the omburtamab moiety binds to B7-H3 expressed on certain tumor cells. Upon binding, lutetium Lu 177-DTPA-omburtamab delivers a cytotoxic dose of beta radiation to B7-H3-expressing cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells but is minimally expressed by normal human tissues. B7-H3 is a negative regulator of T-cell activation; its overexpression plays a key role in immuno-evasion, tumor cell invasion and metastasis, and is correlated with poor prognosis.