Sensitization 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). 

The sensitivity enhancement achieved by VPD is determined by the ratio of the substrate area to the area of the detector aperture (analyzed area), provided there is fiill collection of the impurities. This has been demonstrated for Fe and Zn. For Cu and Au, however, only a small percentage can be collected using this technique, due to electrochemical plating. An example comparing direct TXRF with VPD-TXRF on the same substrate is shown in F%ure 4. 

The sensitivity enhancement in the INEPT experiment is particularly marked when nuclei of low magnetogyric ratios are being detected. A comparison of the signal intensities obtained by polarization transfer against those obtained by full NOE for various nuclei is presented in Table 2.1. 

Cross-polarisation (CP) in the rotating frame has been introduced as a means of transferring polarisation between different nuclear species in solids [168], and has become of central importance for obtaining spectra of rare spins with low gyromagnetic ratios such as 13C, since a significant sensitivity enhancement may be achieved. Cross-polarisation can be used either for direct observation of low-sensitivity nuclei or for indirect detection of such nuclear species via high-sensitivity nuclei such as protons [169]. 

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. 

The INEPT (Insensitive Nuclei Enhanced by Polarization Transfer) experiment [6, 7] was the first broadband pulsed experiment for polarization transfer between heteronuclei, and has been extensively used for sensitivity enhancement and for spectral editing. For spectral editing purposes in carbon-13 NMR, more recent experiments such as DEPT, SEMUT [8] and their various enhancements [9] are usually preferable, but because of its brevity and simplicity INEPT remains the method of choice for many applications in sensitivity enhancement, and as a building block in complex pulse sequences with multiple polarization transfer steps. The potential utility of INEPT in inverse mode experiments, in which polarization is transferred from a low magnetogyric ratio nucleus to protons, was recognized quite early [10]. The principal advantage of polarization transfer over methods such as heteronuclear spin echo difference spectroscopy is the scope it offers for presaturation of the unwanted proton signals, which allows clean spec-... 

Fig. 2. Pulse scheme for the gradient-selected, sensitivity-enhanced X/Y se-HSQC experiment as employed for 31P/15N correlation spectroscopy in Ref. 25. 90° and 180° hard pulses are denoted by solid and open bars, respectively. 2 are delays of length 1/(4 /x,y)> and is a short delay of the same length as the gradient pulse (typically rj 1 ms). Pulse phases are x, unless specified. The ratio of gradient pulse strengths is set to G2/Gi = Yy/Yx, and quadrature detection in Fi is achieved by recording every transient twice and changing the sign of G2 in the second scan.

Nitro compounds may add to carbon-centered radicals and thus also with the majority of the DNA radicals (Chap. 6.3 only the very strongly reducing radicals such as eaq and C02 reduce the nitro sensitizers to (unstable) hydroxyl-amines McClelland et al. 1984). Originally, the nitro compounds and 02 have just been taken as oxidants irrespective of their mode of action, especially as the efficiency of the sensitizers correlates with their reduction potential (Adams and Cooke 1969 Tallentire et al. 1972 Simic and Powers 1974 Adams et al. 1976a, 1981). This concept is expressed in relationship (88), where C is the sensitizer concentration required to achieve a constant sensitizing response (e.g. an enhancement ratio of 1.6) and E7 the one-electron reduction potential of the sensitizer at pH 7. 

Reproducibility of the results depends strongly on the signal-to-noise ratio achieved. Therefore, whenever polarization transfer can give some sensitivity enhancement, use of INEPT (or other scheme) for T measurement would increase the precision and save experimental time. It is also possible to measure the relaxation times indirectly through measurements of 29Si satellites in 3H NMR spectra355, but application of the INEPT variant of such measurements is much more straightforward. 

An alternative pulse sequence that provides the same multiplicities as INEPT but with intensity ratios that follow the binomial theorem is DEPT (distortionless enhancement by polarization transfer).The pulse sequence, depicted in Fig. 12.3a, can be used, like refocused INEPT, for sensitivity enhancement but is usually employed as an editing technique. The three evolution periods T are chosen to approximate 1/2/, but the length of the pulse labeled 0 can be varied. As we show in the following, CH has maximum intensity at 0 = 90° CH2 has zero... 

As a quantitative measure of the far-held performance, two quantities may be introduced. First of all, sensitivity enhancement factor (SEF), a ratio of resonance angle shift due to target analyte binding on a nanowire-based biosensor to that of a conventional SPR structure using a thin gold him with equal thickness, is defined as... 

The NMR data acquisition sensitivity depends on the NMR probe performance. Recently, a remarkable sensitivity enhancement was achieved by a cryogenic probe.122 This technology reduces the thermal noise of the NMR signal by cooling the device by liquid helium. In practice, the enhancement strongly depends on the sample condition. Usually, the S/N ratio increases by factors from two to four for protein solution. 

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