title: Reconciliation of tumor dose response to external beam radiotherapy versus radioimmunotherapy with 131iodine-labeled antibody for a colon cancer model.
abstract: Reported doses of external beam radiotherapy and radioimmunotherapy (RIT) to produce equivalent therapeutic effects are inconsistent, with many proposed causes. Calculations of effective dose were performed for the case of LS174T human colon cancer xenografts, where a 60Co single fraction exposure (6 Gy) was matched with 131I-labeled 17-1A monoclonal antibody therapy (300 microCi injection, 19 +/- 2 Gy using the Medical Internal Radiation Dose uniform isotropic model). Measured three-dimensional dose-rate distributions were used to form a time-dependent description of the dose-rate nonuniformity. Included in the calculation of RIT effective dose was energy loss, dose nonuniformity, dose-rate dependence, hypoxic fraction, and cell proliferation. The calculations assumed the linear quadratic model for cell survival with alpha = 0.3 Gy-1, alpha/beta = 15 to 25 Gy, and mu = 0.46 h-1. The biologically effective dose for the single fraction 60Co exposure was 7.4 to 8.4 Gy. Estimates of dose efficiency factors consecutively applied to the RIT dose estimate were: (a) energy loss external to the tumor (x0.85); (b) effect of dose nonuniformity on cell survival (x0.65); and (c) effect of correlation of dose nonuniformity with cell proliferation rate (x1.08). The resulting effective dose for RIT was 11.4 Gy for tumor regrowth. This analysis substantially reconciles external beam radiotherapy/RIT dose-response results for this tumor model to within experimental uncertainties.
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D008962:Models, Theoretical; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D014183:Transplantation, Heterologous
chemical_list: D000912:Antibodies, Neoplasm; D007457:Iodine Radioisotopes