UPTAKE AND RELEASE OF RADIOLABELED MONOCLONAL ANTIBODY-PO66 BY MULTICELLULAR AGGREGATES OBTAINED FROM A LUNG SQUAMOUS CARCINOMA CELL-LINE

Po66, a monoclonal antibody (MAb) directed against lung squamous cell carcinoma, has been shown, when injected intravenously, to be retained for a long time in tumors. This property encouraged trials to use Po6 6 as an agent of metabolic radiotherapy. The suitability of multicellu lr spheroids to reproduce the in vivo conditions of irradiation of tum ors by Po66 was investigated in the present work. Spheroids were forme d from the lung carcinoma cell line SK-MES-1. They resembled morpholog ically small carcinoma nodules with desmosome-like intercellular junct ions at the periphery and a central necrotic core. The cells expressin g the antigen recognized by Po66 had a heterogeneous distribution and were predominant in the outer layers of the cell aggregates. Spheroids were exposed to radiolabelled Po66. The MAb diffused slowly and reach ed a maximal incorporation after 4-12 hours incubation. A control unre lated antibody did not penetrate appreciably. Autohistoradiographic ex periments suggested that the antibody accumulated in most cells expres sing the antigen. The rate of MAb release from the spheroids was very low (T1/2 = 163 h). Taken together, the data indicate that spheroids m ight be a relevant model to investigate the parameters controlling Po6 6-mediated immunoradiotherapy.