A method to predict response of cell populations to cocktails of chemotherapeutics and radiopharmaceuticals: Validation with daunomycin, doxorubicin, and the alpha particle emitter 210Po

John M. Akudugu, Roger W. Howell

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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. Methods: Cells 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 basis of individual cell incorporation of each cytotoxic agent and validated by direct comparison with the experimental clonogenic cell survival. Results: Both daunomycin and doxorubicin enhanced the toxicity of the α-particles with a magnitude greater than expected based on single-agent toxicities. Cell survival obtained by Monte Carlo simulation was in good agreement with clonogenic cell survival for the combination treatments. Conclusion: Flow cytometry assisted Monte Carlo simulations can be used to predict toxicity of cocktails of α-emitting radiopharmaceuticals and chemotherapy drugs in a manner that takes into account the effects of nonuniform distributions of agents within cell populations.

Original languageEnglish (US)
Pages (from-to)954-961
Number of pages8
JournalNuclear Medicine and Biology
Volume39
Issue number7
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Keywords

  • Alpha particle
  • Chemotherapy
  • Drug cocktail
  • Monte Carlo
  • Radionuclide therapy

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