A Method to Predict Response of Cell Populations to Cocktails of Chemotherapeutics and Radiopharmaceuticals: Validation with Daunomycin Doxorubicin and the Alpha Particle Emitter 210Po

摘要

There is considerable interest in the use of α-emitting radionuclides in radioimmunotherapy. However, the high toxicity of α-emitting radionuclides often does not permit administration of high activities for fear of normal tissue toxicity. Accordingly, targeting procedures need to be optimized for improved tumor control and minimized normal tissue toxicity. To guide design of effective cocktails of α-emitting radiopharmaceuticals and chemotherapy drugs, approaches that can predict biological response of a cell population on a cell-by-cell basis are needed.MethodsCells were concomitantly treated with the α-particle emitting radiochemical ²¹⁰Po-citrate and daunomycin, or with ²¹⁰Po-citrate and doxorubicin. The responses of the treated cell populations were measured with a colony forming assay. The nonuniform cellular incorporation of the radiochemical and drugs was determined simultaneously on a cell-by-cell basis using flow cytometry. Monte Carlo methods were used to simulate cell survival on the of basis individual cell incorporation of each cytotoxic agent and validated by direct comparison with the experimental clonogenic cell survival.