Protective effects of a novel perfluorochemical emulsion in photodynamic therapy.

The effects of pre-injection of mice with a novel perfluorodecalin-based emulsion on the responses to photodynamic therapy (PDT) using the photosensitizer, metatetra (hydroxyphenyl) porphyrin (m-THPP), have been studied. Injection of emulsion after m-THPP and before illumination (activating wavelength 648 nm) protected skin against PDT-induced inflammatory effects, as reflected by decreases (P less than 0.05) in vascular permeability and oedema formation. However, there was no protection against epidermal cell loss. In contrast, injection of emulsion before sensitizer had no corresponding effect. A fall in mean dermal temperature of up to 6 degrees C occurred in mice injected with emulsion 1-2.5 h before illumination suggesting a decrease in skin blood flow which would reduce oedema formation. Possible mechanism(s) for this apparent protective effect are discussed.

Perfluorochemicals and photodynamic therapy in mice.

The effects of pre-treatment with a novel PFC emulsion on PDT-induced tumor necrosis have been studied in mice. Injection of emulsion either 2.5 hr or 24 hr before PDT did not affect the depth of tumour necrosis. However, pre-treatment with the emulsion appeared to protect skin against photodynamic damage although the mechanism(s) and active principle(s) involved were not identified. These results suggest that there may be specific advantages in using emulsified PFCs in conjunction with PDT which may be independent of changes in tumour oxygenation.

meso-Tetra(hydroxyphenyl)porphyrins, a new class of potent tumour photosensitisers with favourable selectivity.

We compared para-, meta- and ortho-isomers of meso-tetra(hydroxyphenyl)porphyrin (p-, m- and o-THPP) and the potassium salt of the para compound (K-p-THPP) with haematoporphyrin derivative (HpD) and Photofrin II in their ability to sensitise tumours, skin and brain to light. HpD and Photofrin II induced modest tumour photosensitisation at the cost of substantial skin and brain sensitisation. At doses low enough to keep sensitisation of these normal tissues within acceptable limits, tumour sensitisation was sufficient to give necrosis only approximately 2 mm deep after exposure to 10 J cm-2 light. In contrast, doses of p-THPP, K-p-THPP and m-THPP that produced skin and brain sensitivity within acceptable limits sensitised tumours enough to give 4-9 mm necrosis after 10 J cm-2 light. m-THPP was, on a molar basis, about 25-30 times as potent as HpD and Photofrin II in sensitising tumours. o-THPP was also a potent tumour photosensitiser, but induced a prohibitive degree of skin photosensitivity even at low doses. It is unlikely that these differences in relative selectivity are due to differences in such photophysical parameters as optimum activating wavelength (which would affect tissue penetration by light), or light absorption, and physicochemical factors that determine tissue localisation may be involved. The high tumour sensitising potency and favourable tissue selectivity of m-THPP, p-THPP and K-p-THPP make them promising candidates for clinical tumour phototherapy.