Tumor-to-normal-tissue ratio

From Ref. (Ill), tumor-to-normal tissue ratios measured 24-h post 30-mg/kg i.p. injection, endpoint of tumor growth 3 cm . Noncompartimental analjfsis of biological half-life in BDIX rats, from Ref. (112). 

What tumor-to-normal-tissue ratios can be achieved with microsphere therapy ... 

The literature reports a hroad range of tumor-to-normal tissue ratios (T/N) of MAA observed in malignant lesions ranging from 0.1 (that is, less uptake within the tumor than in normal tissue) to 26.5 times higher uptake in tumor than in unaffected liver cells [29] with a mean T/N between 4 and 5. This is in line with our results showing a range from 0.1 to 12.4 with a mean and standard deviation of 3.8 2.3. 

In semiquantitative methods, static images are utilized as in visual assessment to determine the tissue activity and compare the relative tumor uptake. One method uses an index, the tumor-to-normal tissue activity ratio (T/N), using data from the normal and tumor regions on the reconstructed images. The ratios are independent of the administered dosage, patient s weight or blood glucose level. The T/N ratio assessment is somewhat similar to visual assessment. The choice of an appropriate normal reference site, particularly in the abdomen and pelvic area, is critical in this analysis. 

BODIPY fluorescence (Figure 31). These particular properties minimize the background signal and lead to a better tumor-to-normal tissue signal ratio in fluorescence microscopy imaging experiments (Figure 32). The process was also shown to be reversible and, after treatment of tumors with ethanol, the fluorescence disappeared. Since this probe turns off when the cells die, this fluorescence... 

The successful application of boron neutron capture therapy (BNCT) is dependent on the identification and preparation of boron-containing compounds that can be delivered to and retained by the tumor in significant amounts (>15 pg boron/g tumor) (Fairchild and Bond, 1985). Compounds targeted for application in BNCT must either accumulate in the tumor through natural mechanisms or, in the case of compounds that have no natural propensity for the tumor, be delivered to the tumor using a tumor-specific delivery modality. In addition to the required tumor boron concentration, the selected compounds should yield in vivo biodistributions with tumor to normal tissue (including blood) ratios of three or higher and be sufficiently nontoxic (Hawthorne, 1993 Soloway et al., 1998). 

Specific targeting of radioisotopes or toxic drugs to tumors for cancer detection and treatment is an enticing but elusive goal. It has proved difficult to achieve adequate concentration ratios between tumor and normal tissues to improve on standard diagnostic and therapeutic methods. 

To perform photodynamic therapy (PDT) in skin tumors, the most often used substance is ALA. The porphyrin precursor is topically applied under occlusive foil as described above. Irradiation should be performed when the optimal ratio of photosensitizer levels between tumor and normal tissue is reached (in the case of ALA 2-6 h after application Figures 2, 5, 7) [16]. The type of light source (laser or incoherent light) and the required fluence depend on the photosensitizer used as well as on the type and localization of the lesion. 

The first generation photosensitiser Hematoporphyrin derivative (HPD) is a complex mixture of various porphyrins [9], which was used for most of the basic experimental work and almost exclusively in the clinical brain tumor studies. HPD has its optimum absorption between 628 and 632 nm and allows penetration depths up to 7 mm depending on the tissue [37,38]. The dose in clinical use is 2 mg kg injected intravenously. Energies required range from 60 to 260 J cm. The ratio of the concentration in tumor to normal brain ranges from 2.5-4 1 and in animal experiments it ranges up to 12 1 [39,40]. 

Moreover, the radiation from this Isotope allows Its use In presently available radlosclntlgraphlc equipment. A series of precursor complexes Involving Ru(II) and Bu(III), which could be used to coordinate a range of nitrogen-containing biochemical ligands and macromolecules such as proteins and nucleic acids, seems possible. Finally, Improvement of the tumor localization, already exhibited by some ruthenium complexes, based on the elevated Ru(IT)/Ru(III) ratios hypothesized to occur In tumor relative to normal tissue may make available a new class of tumor-lmaglng pharmaceuticals. 

Fig. 3 Fluorescent optical imaging of tumor with bombesin-Cy 5.5-N-acetylhistidme-glycol chitosan nanoparticles (BC-NAHIS-GC). (a) BC-NAHIS-GC nanoparticle, (b) Chemical structure of BC-NAHIS-GC. (c) In vivo noninvasive fluorescent imaging of mice with PCS tumors C-NAHIS-GC (upper) and BC-NAHIS-GC (lower), (d) Ex vivo quantification of fluorescence in tumor tissue (tumor to normal ratio). From Lee et al. [34]...

The concept of the therapeutic ratio is key here as it implies that the effect of the combination therapy is greater in the tumor than in the relevant normal tissues within the treated radiation volume. The therapeutic ratio is often described in a mathematical formulation as the ratio of dose enhancement factors in the tumor divided by that in the normal tissues. The following are clear examples of clinical situations where the use of concurrent therapy has been found to be associated with an improvement in the therapeutic ratio. 

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