Abstract
The effect of combining photodynamic therapy (PDT) and bioreductive drugs has been investigated using the RIF-1 experimental murine tumour. Light was delivered interstially to the tumour at 675 nm using a single optical fibre attached to an argon-ion dye laser. The photosensitizer was disulphonated aluminium phthalocyanine (AlS2Pc) and the bioreductive drugs were the dual function nitroimidazole RSU1069 and its pro-drug RB6145. Varying the time between administration of the photosensitizer and light delivery (TL) from 30 min to 24 h had little influence on the extent of the anti-tumour effect of PDT alone, as measured by the regrowth delay endpoint. When the bioreductive drug was included in the treatment, administered 20 min before light irradiation, regrowth delay was greatly increased. The effectiveness of the combined treatment was optimum for short values of TL (about 1 h). Fluorescence microscopy was used to investigate the distribution of the photosensitizer within the tumours. This showed that the compound was mainly confined to the tumour vasculature over the first few hours post-treatment. The high efficacy of the combined treatment of PDT and bioreductive drugs for short values of TL suggest that photodynamic action, during the period when the photosensitizer AlS2Pc is confined to the vasculature, enhances the severity of tumour hypoxia which is sufficient to induce activation of the bioreductive drugs.
Highlights
The design of this study was based on the hypothesis that photodynamic therapy (PDT) delivered whilst the sensitiser is confined mainly to the vasculature, would induce a more severe degree of hypoxia and should aid the effectiveness of the bioreductive agent
Some experiments were carried out using fluorescence microscopy (CCD) in the RIF tumours of the size range of those used for the PDT experiments
AlS2Pc is an effective photosensitiser for the RIF-1 tumour when used at a dose of 4.37 mg kg' administered from 20 min to 24 h before laser treatment
Summary
The RIF-1 murine sarcoma line was maintained as described previously (Twentyman et al, 1980; Stratford et al, 1988). 2 x 105 cells suspended in 0.05 ml PBS were implanted intradermally (i.d.) into the mid-dorsal pelvic region of 8-10 week old C3H/He mice (category IV). The tumour volume at treatment was 100-200 mm. Tumours were measured in three orthogonal directions at 2-day intervals. The tumour volume was calculated using the geometric mean of these measurements and assuming spherical geometry. The regrowth endpoint was the time taken for the tumours to grow to four times their volume at the start of treatment
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