anti-mesothelin antibody, by PET imaging and biodistribution studies

article Cu labeling NOTA Mesothelin Amatuximab Antibody Tumor targeting Objectives: Toinvestigate theeffect of the injection doseof MORAb-009(amatuximab, ananti-mesothelin mono- clonal antibody), the tumor size and the level of shed mesothelin on the uptake of the antibody in mesothelin- positive tumor and organs by biodistribution (BD) and positron emission tomography (PET) imaging studies. Methods: 2-S-(4-Isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) was con- jugated to amatuximab and labeled with 64 CuCl2 in 0.25 M acetate buffer, pH 4.2. The resulting 64 Cu-NOTA- Cu-NOTA-amatuximab (10 μCi) containing a total amatuximab dose of 2, 30, or 60 μg. The BD and PET imaging were also investigated 3, 24 and 48 h after injecting a total dose of 30 μ g( 10μ Ci for BD), and 2o r 60μ g( 300μCi for PET), respectively. Results: Comparing the results of the BDs from three different injection doses, the major difference was shown in the uptake(%ID/g)of the radiolabel intumor,liver and blood. The tumor uptake and bloodretention from30and 60 μg doses were greater than those from 2 μg dose, whereas the liver uptake was smaller. The BD studies also demonstrated a positive correlation between tumor size (or the level of shed mesothelin in blood) and liver up- take. However, there was a negative correlation between tumor size (or the shed mesothelin level) and tumor uptake and between tumor size and blood retention. These findings were confirmed by the PET imaging study, which clearly visualized the tumor uptake with the radiolabel concentrated in the tumor core and produced a tumor to liver ratio of 1.2 at 24 h post-injection with 60 μg amatuximab, whereas the injection of 2 μg