Radiation sensitizer enhancement ratio

Cisplatin was first characterized as a radiation sensitizer using hypoxic Bacillus megaterium spores (53). Radiation sensitization by cisplatin was confirmed in vegetative Escherichia coli with a maximum sensitizer enhancement ratio of 1.77 in anoxic bacteria at a cisplatin concentration of 50 uM (54). Zimbrick et al. (55) extended these studies to other platinum complexes. The earliest studies in mammalian cells used hypoxic V-79 Chinese hamster cells and showed a small radiation sensitization with 8 iM of cisplatin (56). Nias and Szumiel (57) first reported that pretreatment of Chinese hamster ovary (CHO) cells with a platinum complex could sensitize well-oxygenated cells to radiation. Wodinsky etal. (58) showed that cisplatin potentiated the effect of whole-body radiation therapy in mice inoculated intraperitoneally with P388 leukemia compared with either modality alone. Therapeutic potentiation was found in MTG-B subcutaneous tumors and intracerebral RBT when the animals were treated with cisplatin and radiation (59). 

In vitro studies have shown that paclitaxel is a potent radiation sensitizer. Survival curves using grade 3 human astrocytoma cell lines showed a sensitizer enhancement ratio of 1.8 (57). In a series of experiments using a human leukemic cell line (HL-60), a sensitizing enhancement ratio of 1.48 was noted (58). Other studies have shown that G2/M block is not the only mechanism of paclitaxel-induced radiosensitization (59). 

Preincubation of A549 and HT29 cells with 2.5 pM SAHA under aerobic conditions followed by 1 h anoxia under which radiation was performed resulted in a sensitizer enhancement ratio at 0.01 survival levels (SERo.oi) of 1.33 and 1.59, respectively (Figure 6). 

Another proposal is that radiosensitization embarks from 5-FU-induced cell cycle redistribution. Both 5-FU and FdUrd result in arrest of S phase cells and block cells that are notinS phase at the Gl/S interface. Studies in rodent (31) and HeLa cells (32) have revealed that early S phase is a relatively sensitive phase of the cell cycle, thereby suggesting that fluoropyrimidine-mediated radiosensitization may result from redistribution into a more radiosensitization phase of the cell cycle. Investigators also tried to evaluate dependence on the timing of exposure to fluoropyrimidines in relation to radiation on the resultant radiosensitization, such as to correlate the enhancement ratio with the fraction of cells in early S phase (12) (Fig. 5). 

In addition to the above-outlined cytotoxic effects of gemcitabine, it also serves to act as a radiation sensitizer in many cell lines (see Table 1). Depending on the cell line tested, the drug concentration, the schedule of administration, and the cell proliferative status (e.g., plateau vs exponential growth), relative enhancement ratios (RERs) in the range of 1.1-2.5 have been reported. There is no evidence that preferential radiosensitization occurs in more radioresistant cell lines. 

M in concentration. This is in the range required for single-molecule detection. These sensitivity levels have been obtained on colloidal clusters at near-infrared excitation. Figure 10.3 is a schematic representation of a single-molecule experiment performed in a gold or silver colloidal solution. The analyte is provided as a solution at concentrations smaller than 10-11 M, Table 10.1 lists the anti-Stokes/Stokes intensity ratios for crystal violet (CY) at 1174 cm-1 using 830-nm near-infrared radiation well away from the resonance absorption of CY with a power of 106 W/cm2 [34]. CV is attached to various colloidal clusters as indicated in the table. Raman cross sections of 10-16 cm2/molecule or an enhancement factor of 1014 can be inferred from the data. 

The structure of itaconic acid bears some resemblance to methacryllc acid. While It Is know that methacryllc acid and methacrylic anhydride do enhance sensitivity when copolymerized with methyl methacrylate, some of the Increase In speed may be due to porosity (7,12). The gas formation may cause a higher rate of dissolution then can be attributed to chain scission alone. Pittman and co-workers have reported G(s) values for poly(methacryllc anhydride) of 0.4 (10) and 1.8 and 2.9 (14) based on gamma radiation experiments. Hiroaka (12) measured G(s) by gas evolution on Irradiation of films with electron beams and established values In the ration 1 2 6 for the methyl methacrylate. A terpolymer with the three components In the molar ratio of 70 15 15 (same three monomers) was selected by Moreau et al (13) on the basis of complete lithographic evaluation. The speed Is 4 to lOx that of PMMA. As aforementioned, an Increase In G(s) may be only partially responsible. 

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