100 A 10-1 10-2 10 keV 10-3 10-4 10-5 100 100% labeled B 50% labeled 10% labeled 1% labeled Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) 10-1 10-2 10-3 Surviving fraction of labeled cells Supplement B Figure 1. Effect of electron energy and fraction of cells labeled on the shape of the survival curve for the labeled cell population when monoenergetic electron emitters are uniformly distributed among the labeled cells: (A) 10 keV, (B) 30 keV, (C) 100 keV, (D) 300 keV, (E) 1000 keV. Panels A, C, and E are reproduced in Figure 1. The surviving fraction of labeled cells is plotted as a function of mean absorbed dose to the labeled cell nuclei when either 100%, 50%, 10%, or 1% of the cells are labeled. The red and blue dashed lines represent exponential survival curves with D37 = D37,self = 1.2 Gy and D37 = D37,cross = 4.0 Gy, respectively, the values used for these parameters in this figure. At very low energies (10 keV, Panel A), where the cross-dose to the nucleus is negligible, all curves expectantly follow that for D37 = D37,self = 1.2 Gy. As the electron energy increases, the cross-dose increases in proportion to the selfdose, and the curves move toward the dotted blue line corresponding to D37 = D37,cross = 4.0 Gy. However, when only a small percentage (1% and 10%) of the cells are labeled, the self-dose continues to play a key role in determining the surviving fraction of the labeled cells even when the electron energy increases to 1000 keV. This figure highlights the importance that the percentage of labeled cells has on the shape of the labeled cell survival curves. 30 keV 10-4 10-5 100 C 10-1 10-2 100 keV 10-3 10-4 10-5 100 D 10-1 10-2 300 keV 10-3 10-4 10-5 100 E 10-1 10-2 1000 keV 10-3 10-4 10-5 0 20 40 60 80 Mean absorbed dose to labeled cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 1 of 6 MEDICAL PHYSICS TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy 100 50% labeled A 10% labeled 1% labeled Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) 10-1 10-2 10-3 10 keV 10-4 10-5 100 B 10-1 10-2 30 keV 10-3 Surviving fraction of unlabeled cells Supplement B Figure 2. Effect of electron energy and fraction of cells labeled on the shape of the survival curve for the unlabeled cell population when monoenergetic electron emitters are uniformly distributed among the labeled cells: (A) 10 keV, (B) 30 keV, (C) 100 keV, (D) 300 keV, (E) 1000 keV. Panels A, C, and E are reproduced in Figure 2. The surviving fraction of unlabeled cells is plotted as a function of mean absorbed dose to the unlabeled cell nuclei when either 100%, 50%, 10%, or 1% of the cells are labeled. The red and blue dashed lines represent exponential survival curves with D37 = D37,self = 1.2 Gy and D37 = D37,cross = 4.0 Gy, respectively, the values used for these parameters in this figure. At very low energies (10 keV, Panel A), where the crossdose to the nuclei of the unlabeled cells is negligible and therefore there is no killing of unlabeled cells. Cross-dose to the unlabeled cells is significant at 30 keV (Panel B), and killing of these cells depends on the percentage of cells that are labeled. As the electron energy increases, the impact of percent labeling on the response of unlabeled cells diminishes, and the curves move toward the dotted blue line corresponding to D37 = D37,cross = 4.0 Gy. With the exception of 30 keV electrons, this figure shows that the response of the unlabeled cell population is generally independent of the percentage of labeled cells when the activity is distributed uniformly among the labeled cells. 10-4 10-5 100 C 10-1 10-2 100 keV 10-3 10-4 10-5 100 D 10-1 10-2 300 keV 10-3 10-4 10-5 100 E 10-1 10-2 1000 keV 10-3 10-4 10-5 0 20 40 60 80 Mean absorbed dose to unlabeled cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 2 of 6 MEDICAL PHYSICS TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy 100 100% labeled A 50% labeled 10% labeled 1% labeled Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) 10-1 10-2 10-3 10 keV 10-4 10-5 100 B 10-1 Surviving fraction of mixed population of cells Supplement B Figure 3. Effect of electron energy and fraction of cells labeled on the shape of the survival curve for the mixed cell population (labeled + unlabeled) when monoenergetic electron emitters are uniformly distributed among the labeled cells: (A) 10 keV, (B) 30 keV, (C) 100 keV, (D) 300 keV, (E) 1000 keV. Panel B is reproduced in Figure 3. The surviving fraction of the mixed cell population is plotted as a function mean absorbed dose to all cell nuclei when either 100%, 50%, 10%, or 1% of the cells are labeled. The red and blue dashed lines represent exponential survival curves with D37=D37,self=1.2 Gy and D37=D37,cross=4.0 Gy, respectively, the values used for these parameters in this figure. At very low energies (10 keV, Panel A), where the cross-dose to the nucleus is negligible, only the labeled cells are killed so the surviving fraction for 50%, 10%, and 1% survival follow 1-flabeled. At 30 keV, the response of the mixed cells population is highly dependent on the percentage of cells that are labeled (Panel B). As the electron energy increases, the cross-dose increases in proportion to the self-dose, and the curves move toward the dotted blue line corresponding to D37=D37,cross=4.0 Gy. The response of the mixed population to 100 keV electrons continues to depend on percentage labeled (Panel C). However, at 300 keV (Panel D) and 1000 keV (Panel E), the response of the mixed population of cells is relatively independent of the percentage of labeled cells when the radioactivity is uniformly distributed among the labeled cells. 10-2 30 keV 10-3 10-4 10-5 100 C 10-1 10-2 100 keV 10-3 10-4 10-5 100 D 10-1 10-2 300 keV 10-3 10-4 10-5 100 E 10-1 10-2 1000 keV 10-3 10-4 10-5 0 20 40 60 80 Mean absorbed dose to all cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 3 of 6 MEDICAL PHYSICS TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy Supplement B Figure 4. Combined effect of labeled fraction and of activity distribution on the cell survival-response of the labeled cells when monoenergetic electron emitters are lognormally distributed among the labeled cells. The data for 10, 30, 100, 300, and 1000 keV electrons are provided in panels: (A-E) 100% labeled, (F-J) 50% labeled, (K-O) 10% labeled, and (P-T) 1% labeled. The activity distribution is either uniform (σ→0, solid black) or lognormal with shape parameters of σ = 0.6 (solid red), 1.0 (solid green), and 2.0 (solid yellow). The dashed red and blue lines represent exponential survival curves with D37=D37,self=1.2 Gy and D37=D37,cross=4.0 Gy, respectively. 50% labeled 100% labeled 100 1% labeled 10% labeled A F K P 10-1 10-2 10 keV 10-3 10-4 10-5 100 B G L Q Surviving fraction of labeled cells 10-1 10-2 30 keV 10-3 10-4 10-5 100 H C R M 10-1 10-2 100 keV 10-3 10-4 10-5 100 I D S N 10-1 10-2 300 keV 10-3 10-4 10-5 100 Uniform ( = 0) Lognormal ( = 0.6) Lognormal ( = 1.0) Lognormal ( = 2.0) Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) 10-1 10-2 10-3 J E T O 1000 keV 10-4 10-5 0 20 40 60 80 0 20 40 60 Mean absorbed dose to all cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 4 of 6 MEDICAL PHYSICS 80 0 20 40 60 80 0 20 40 60 80 Mean absorbed dose to all cell nuclei (Gy) TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy Supplement B Figure 5. Combined effect of labeled fraction and of activity distribution on the cell survival-response of unlabeled cells when monoenergetic electron emitters are lognormally distributed among the labeled cells. The data for 10, 30, 100, 300, and 1000 keV electrons are provided in panels: (A-E) no data provided because 100% are labeled, (F-J) 50% labeled, (K-O) 10% labeled, and (P-T) 1% labeled. The activity distribution is either uniform (σ→0, solid black) or lognormal with shape parameters of σ = 0.6 (solid red), 1.0 (solid green), and 2.0 (solid yellow). The dashed red and blue lines represent exponential survival curves with D37=D37,self=1.2 Gy and D37=D37,cross=4.0 Gy, respectively. 50% labeled 100% labeled 100 1% labeled 10% labeled A F K P 10-1 10-2 10 keV 10-3 10-4 10-5 100 B G L Q Surviving fraction of unlabeled cells 10-1 10-2 30 keV 10-3 10-4 10-5 100 H C R M 10-1 10-2 100 keV 10-3 10-4 10-5 100 I D S N 10-1 10-2 300 keV 10-3 10-4 10-5 100 J E T O 10-1 10-2 1000 keV 10-3 10-4 10-5 0 20 40 60 80 0 20 40 60 Mean absorbed dose to all cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 5 of 6 MEDICAL PHYSICS 80 0 20 40 60 80 0 20 40 60 80 Mean absorbed dose to all cell nuclei (Gy) TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy Supplement B Figure 6. Combined effect of labeled fraction and of activity distribution on the cell survival-response of a mixed population of cells (labeled and unlabeled) when monoenergetic electron emitters are lognormally distributed among the labeled cells. The data for 10, 30, 100, 300, and 1000 keV electrons are provided in panels: (A-E) 100% labeled, (F-J) 50% labeled, (K-O) 10% labeled, and (P-T) 1% labeled. The activity distribution is either uniform (σ→0, solid black) or lognormal with shape parameters of σ = 0.6 (solid red), 1.0 (solid green), and 2.0 (solid yellow). The dashed red and blue lines represent exponential survival curves with D37=D37,self=1.2 Gy and D37=D37,cross=4.0 Gy, respectively. 50% labeled 100% labeled 100 1% labeled 10% labeled A K F P 10-1 10-2 10 keV 10-3 Surviving fraction of mixed population of cells 10-4 10-5 100 B L G Q 10-1 10-2 30 keV 10-3 10-4 10-5 100 H C R M 10-1 10-2 100 keV 10-3 10-4 10-5 100 I D S N 10-1 10-2 300 keV 10-3 10-4 10-5 100 Uniform ( = 0) Lognormal ( = 0.6) Lognormal ( = 1.0) Lognormal ( = 2.0) Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) 10-1 10-2 10-3 J E Uniform ( = 0) Lognormal ( = 0.6) Lognormal ( = 1.0) Lognormal ( = 2.0) Exp. (D37 = 1.2 Gy) Exp. (D37 = 4.0 Gy) T O 1000 keV 10-4 10-5 0 20 40 60 80 0 20 40 60 Mean absorbed dose to all cell nuclei (Gy) - Vol. - No. - Month Year Supplement B, Page 6 of 6 MEDICAL PHYSICS 80 0 20 40 60 80 0 20 40 60 80 Mean absorbed dose to all cell nuclei (Gy) TARGETED & NON-TARGETED CELLS – Rajon et al. Figures for D37,self = 1.2 Gy, D37,cross = 4.0 Gy