Photodynamic therapy with WST09 (Tookad): Quantitative studies in normal colon and transplanted tumours

Abstract

Photodynamic therapy (PDT) is attracting increasing interest for the safe destruction of localised tumours in a range of organs. However, most photosensitising drugs require a delay of hours to days between drug administration and light activation with skin photosensitivity that may last for weeks. WST09 (Tookad) is a new faster acting photosensitiser that clears within a few hours. In normal rat colon, after sensitisation with an intravenous bolus of WST09, light was delivered to a single point on the mucosa and the extent of PDT necrosis measured 3 days later. The lesion diameter was greatest with the highest dose of drug and light and the shortest drug light interval (DLI), falling rapidly with a DLI more than 5 min. In tumours transplanted subcutaneously or into the colon, the extent of necrosis only started falling with a DLI greater than 15 min, suggesting a possible window for tumour selectivity. Histological changes 3 days after PDT were essentially the same as those seen with longer acting photosensitisers. The lesion dimensions were comparable to the largest ones seen with other photosensitisers under similar experimental conditions. We conclude that WST09 is a powerful photosensitiser that produces PDT effects similar to those seen with longer acting drugs, but with the major advantages of a short DLI and rapid clearance. ' 2005 Wiley-Liss, Inc.Key words: photodynamic therapy; palladium bacteriopheophorbide; colon; colon cancer Photodynamic therapy (PDT) is attracting increasing interest for the treatment of a range of malignant and nonmalignant diseases. It involves the production of localised areas of necrosis with light after the prior administration of a photosensitising drug in the presence of oxygen. The main attraction of PDT is the nature of the biological effect. No heat is involved, so there is essentially no effect on connective tissues like collagen and elastin. Thus the mechanical integrity of hollow organs like the colon is maintained at all stages of healing, even in the presence of full thickness necrosis in the wall of the organs. It also means that treated areas heal well, often with less scarring than after other local insults such as heat, which does destroy connective tissues and usually leads to at least some scarring. 1 Furthermore, there is no cumulative toxicity, so treatment can be repeated at the same site, unlike radiotherapy.Early reports of PDT suggested that photosensitising drugs were taken up selectively in malignant tissue, which raised the possibility of selective destruction of cancers. Undoubtedly, there is some degree of selectivity of uptake, but the ratio of drug concentration between tumours and the adjacent normal tissue in which they arose is often no more than 2-3:1. 2 This difference is rarely enough to get worthwhile selectivity of necrosis when tumour and normal tissue are exposed to the same light dose, as is inevitably the case when treating the region where normal and tumour tissues meet. 3 Many studies have been undertaken to optimise the time interv...

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