Successful application of anticancer therapy, and especially photodynamic therapy (PDT) mediated by type I1 (PDTII) processes, depends on the oxygen content within the tumor before, during and after treatment. The high consumption of oxygen during type I1 PDT imposes constraints on therapy strategies. Although rates of oxygen consumption and repletion during PDTII were suggested by theoretical studies, direct measurements have not been reported. Application of a novel oxygen sensor allowed continuous and direct in sifu measurements (up to a depth of 8-9 mm from the tumor surface and for several hours) of temporal variations in the oxygen partial pressure (pOz) during PDT. Highly pigmented M2R mouse melanoma tumors implanted in CD1 nude mice were treated with bacteriochlorophyll+erine (Bchl-Ser; a new photodynamic reagent) and were subjected to fractionated illumination (700 < A < 900 nm) at a fluence rate of 12 mW cm+. This illumination led to total oxygen depletion with an average consumption rate of 7.2 pM(Oz) s-l. Spontaneous reoxygenation (at an average rate of 2.5 pM(O,)/s) was observed during the following dark period. These rates are in good agreement with theoretical considerations (Foster et al., Radiat. Res. 126, 296,1991 and Henning et al., Radiut. Res. 142,221,1995). The observed patterns of oxygen consumption and recovery during prolonged periods of Iightldark cycles were interpreted in terms of vasculature damage and sensitizer clearance. The presented data support the previously suggested advantages of fractionated illumination for type I1 photodynamic processes.
Longitudinal and transverse relaxation rates for the 11B resonances in sodium borocaptate (BSH) at varying concentrations were measured in undiluted horse serum in a 4.7 Tesla field. The results could be fit by a model that assumes fast exchange of the BSH molecule between a free and a bound state, using values of 0.77+/-0.7 MHz for the 11B quadrupole coupling constant and (6.3+/-0.9) x 10(-9) s for the rotational correlation time in the bound state. These results were used as a basis for assessing the requirements and limitations of quantitative determination of BSH concentrations in vivo, using 11B NMR. Surface coil 11B NMR spectroscopy was performed on a total of 14 mice injected with BSH. Some of the animals (n=9) had implanted M2R melanoma tumors grown to various sizes in the rear thigh, in which case the surface coil was placed against the tumor, whereas for the other animals (without tumor), the coil was placed against the rear thigh muscle. NMR spectra were acquired under fully relaxed conditions. The spectra were quantitated by peak integration; apparent absolute BSH concentrations were derived by comparison with spectra from a phantom with known BSH concentration, using extrapolation of the time-domain data to zero preacquisition delay. The results indicate significantly higher 11B BSH signal intensities in tumors, compared with muscle tissue, whereas the uptake and clearance kinetics were similar.
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