13II-Anticarcinoembryonic Antigen Therapy of LS174T Human Colon Adenocarcinoma Spheroids1

I.SI74T human colon adenocarcinoma multiceli spheroids were used to study the radiobiological aspects of radioimmunotherapy. The spher oids were incubated in "'I-anticardnocmbrymmantigen (B7) at an antibody concentration of 0.5 ftg/ml and at "'I concentrations of 2.5 and 7.5 fiCi/ml. After incubation times of 90 h, clonogenic cells per spheroid were reduced by 1400-fold and 23-fold at the high and low "'I concen trations, respectively. '"I Nonspecific antibody (PX63) resulted in 2and 1.2-fold reductions. Spheroid diameter was not significantly affected by therapy but histolÃ3gica! examination revealed that there had been a significant reduction in the cell density, particularly near the spheroid surface. Using a theoretical model to estimate radiation dose, a radiation survival curve was constructed. The resulting curve was somewhat con cave suggesting the presence of a resistant population of cells. It is likely that this observation is primarily due to the fact that the inner cells received a lower dose than the outer cells. A population of radiobiologically hypoxic cells in the inner portion of the spheroids may also have contributed to the decreasing slope of the curve as well as ongoing cell division leading to new cells which receive a lower radiation dose per cell cycle. Because of the ability to estimate radiation dose for a given biological effect, these types of experiments may allow predictions of the efficacy of radiolabeled antibody therapy for micrometastatic disease.