Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.

Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with 177Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and 177Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1–2 days p.i., while found in and around necrotic ...