Retention and processing of the monoclonal anti-prostate E4 antibody after binding to prostatic adenocarcinoma DU 145 cells.
Cellular retention and processing of a radiolabelled monoclonal anti-prostate antibody were evaluated after binding to prostatic adenocarcinoma DU 145 cells. An endocytosis assay revealed that the rate of release of radioactivity from the cells had an initially rapid phase within the first hours after antibody incubation, which was presumably due to release of monovalently bound antibodies. This was followed by a slower phase, with the possible release of intact bivalently bound antibodies and excretion of degraded internalized antibodies. The relative amount of released radioactivity of high molecular mass was high, indicating that the major part of the antibodies were released without being internalized and degraded. However, when only the radiolabelled antibody that remained cell-associated after 2 h and longer was considered, a substantial part was found to be internalized and radioactive degradation products were excreted. About 30% of the initially cell-associated radioactivity still remained associated with the cells after 48 h, indicating a rather slow antibody processing, which is favourable if the antibody is to be used for targeted radiotherapy. The retention of cell-associated radioiodine was very similar irrespective of whether the antibodies were radiolabelled with the direct chloramine-T method or the indirect ATE (succinimidyl based reagent) method. Since the ATE method can be used to form stable antibody constructs with the therapeutically relevant alpha-emitting radionuclide, astatine-211, this was an interesting finding that will be further evaluated in the future.
Essand
M
M
Department of Diagnostic Radiology, Uppsala University, Sweden.
Lögdahl
P
P
Nilsson
S
S
Wartenberg
M
M
Acker
H
H
Carlsson
J
J
D000230:Adenocarcinoma / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D011467:Prostate / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000473:pathology*
D000911:Antibodies, Monoclonal