Our anti-CA19-9 antibody radionuclide conjugates (ARCs) contain an anti-CA19-9 monoclonal antibody and site-specifically conjugated chelator bundles, each carrying DOTA groups. They are homogeneous, having 6 or 8 DOTA groups per molecule, and exhibit superior in vitro and in vivo stability.
The radiolabeling efficiency with 111In and 177Lu is over 90% using routine procedures. In mouse models with transplanted human pancreatic BxPC3 tumor cells, 111In-labeled anti-CA19-9 ARC demonstrated excellent immuno-SPECT/CT imaging of tumor mass, with high tumor-to-blood ratio. 177Lu-labeled anti-CA19-9 ARC could inhibit tumor growth with either a single dose or multiple doses, suggesting its potential application for treating pancreatic cancer in humans.
The therapeutic effects of 177Lu-labeled anti-CA19-9 ARC are not hindered by the presence of CA19-9 antigen in the blood. Moreover, its administration can be combined with pre-dosing of a large excess of unlabeled anti-CA19-9 ARC.
The immuno-SPECT/CT imaging of an NU/NU mouse bearing a BxPC3 xenograft tumor by 111In-labeled anti-CA19-9 ARC.
Tumor suppression in NU/NU mice bearing BxPC3 tumor xenografts after three injections of 177Lu-labeled anti-CA19-9 ARC. (Dashed line: tumor volume reached 170 mm3 on day 22 post tumor cell implantation; green triangles: drug administered on day 22, 29 and 36).