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¹³¹I-Anticarcinoembryonic Antigen Therapy of LS174T Human Colon Adenocarcinoma Spheroids¹

University of Rochester Cancer Center, Rochester, NY 14642 [V. K. L., J. K. M., R. M. S.] and Institute of Biochemistry, University of Lausanne, Switzerland [F. B.]

LS174T human colon adenocarcinoma multicell spheroids were used to study the radiobiological aspects of radioimmunotherapy. The spheroids were incubated in ¹³¹I-anticarcinoembryonic antigen (B7) at an antibody concentration of 0.5 µg/ml and at ¹³¹I concentrations of 2.5 and 7.5 µCi/ml. After incubation times of 90 h, clonogenic cells per spheroid were reduced by 1400-fold and 23-fold at the high and low ¹³¹I concentrations, respectively. ¹³¹I Nonspecific antibody (PX63) resulted in 2- and 1.2-fold reductions. Spheroid diameter was not significantly affected by therapy but histological 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 concave 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.

¹ Research supported by the Wilmot Foundation and the H. Gardner and S. Edelman Foundation.

² To whom requests for reprints should be addressed at University of Chicago Center for Radiation, 5841 South Maryland Avenue, Box 442, Chicago, IL 60637.

³ Present address: Michael Reese/University of Chicago Center for Radiation Therapy, Department of Radiation Oncology, 5841 South Maryland Avenue, Box 442, Chicago, IL 60637.

⁴ Present address: SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025

Received 12/13/88. Revised 3/13/89. Accepted 3/21/89.

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