Biomedical subjects

Thomas H Foster

Publications and source records attributed to Thomas H Foster.

22 records · Page 2Linked to original sources

PubMedDate not supplied

Photophysical parameters, photosensitizer retention and tissue optical properties completely account for the higher photodynamic efficacy of meso-tetra-hydroxyphenyl-chlorin vs Photofrin.

Meso-tetra-hydroxyphenyl-chlorin (mTHPC) is one of the most potent photosensitizers currently available for clinical photodynamic therapy (PDT). However the reason or reasons for its high photodynamic efficacy remain(s) unresolved. To investigate the PDT efficacy of mTHPC vs Photofrin we use the knowledge of photophysical parameters extracted from the analysis of oxygen electrode measurements in spheroids to compute and compare their respective singlet oxygen (1O2) dose depositions. The electrode measurements indirectly report the bleaching kinetics of mTHPC and indicate that its photobleaching mechanism is consistent with 1O2-mediated reactions. mTHPC's photodegradation via 1O2 reactions is confirmed by a more direct evaluation of the spatially resolved fluorescence in confocal sections of intact spheroids during irradiation. The PDT efficacy comparisons establish that mTHPC's enhanced potency may be accounted for completely on the basis of its ability to sequester tightly in cells and its photophysical properties, in particular its higher extinction coefficient at a redshifted wavelength. We extend the efficacy comparison to include the influence of hemoglobin absorption of PDT treatment light and show that incorporating the influence of wavelength-dependent light attenuation in tissue further contributes to significantly higher efficacy for mTHPC- vs Photofrin-PDT.

Dihematoporphyrin Ether↗

PubMedDate not supplied

Temporally and spatially heterogeneous distribution of mTHPC in a murine tumor observed by two-color confocal fluorescence imaging and spectroscopy in a whole-mount model.

Efficient intratumor delivery of anticancer drugs and photosensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole-mount two-color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 mum diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.

Animals↗

PubMedDate not supplied

Fluorescence anisotropy imaging reveals localization of meso-tetrahydroxyphenyl chlorin in the nuclear envelope.

We have measured the intrinsic fluorescence anisotropies of six photosensitizers in homogeneous solution, and we have imaged the anisotropies of these sensitizers in tumor cell monolayers using polarization-sensitive laser-scanning confocal microscopy. The intrinsic anisotropies are unremarkable and are within the approximate range of 0.2-0.27. In cells, however, very interesting behavior is exhibited by meso-tetrahydroxyphenyl chlorin (mTHPC). Polarization-sensitive images of mTHPC's fluorescence show a pronounced banding of alternating high and low anisotropy consistent with an ordering of the sensitizer in the nuclear envelope, indicating that this structure is a target of photodynamic damage with this sensitizer. None of the other sensitizers exhibits localization to the nuclear envelope. The frequency distributions of the intracellular anisotropies of the sensitizers exhibit variable peaks and widths. An unusual case is that of Photofrin, with a peak in its anisotropy frequency distribution of -0.12. The change from a positive intrinsic anisotropy in homogeneous solution to a negative value in cells suggests an environmentally induced change in the relative orientations of the absorption and emission dipole moments.

Animals↗

PubMedDate not supplied

Endovascular treatment using low-power ultraviolet laser for delayed vasospasm in the rabbit carotid artery model.

BACKGROUND AND PURPOSE: We previously reported that pretreatment with external ultraviolet (UV) irradiation at 325 nm before blood exposure prevented the development of chronic vasospasm in rabbit common carotid arteries. The purpose of this study was to investigate the preventive effect of endovascular UV light on vasospasm after blood immersion by using the same animal model. METHODS: The right common carotid arteries in 63 rabbits were enclosed in silicon cuffs on day 0. Sheaths were empty or filled with clotted blood. Thirty minutes after the placement of the sheaths, either alone or with blood, the common carotid arteries were subjected to UV or visible light (442 nm) irradiation via an endovascular approach at a fluence rate of 0.17 W/cm(2). The animals were killed on day 2, 9, or 30. Digital subtraction angiography was performed on days 0 and 2 and at the end point to evaluate the degree of vasospasm. RESULTS: UV treatment significantly prevented the development of vasospasm on day 2. On days 9 and 30, there were no significant differences between UV-treated animals and control animals. The preventive effect reached an approximate plateau with an irradiation time of 10 s. No severe vascular injury, such as perforation, occurred in response to UV treatment during the observation period. UV light was significantly more effective than visible light in preventing vasospasm (P <.001). CONCLUSION: These results suggest that endovascular UV irradiation after blood exposure has a prophylactic effect on vasospasm and suggest a dependence on irradiation wavelength and duration of irradiation.

Animals↗