title: The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population.
abstract: Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10(4) clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, 5758 S. Maryland Ave., MC 9006, Chicago, IL 60637, USA. roeske@rover.bsd.uchicago.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Roeske
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Stinchcomb
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use*; D000818:Animals; D002467:Cell Nucleus / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured