Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation

Abstract

Summary Photodynamic therapy (PDT) involves the interaction of light with an administered photosensitising agent to produce cellular destruction. It has promising potential for the local and endoscopic treatment of gastrointestinal cancer. There is however little data on the response of normal intestine to PDT.We have investigated the use of a new photosensitiser chloro aluminium sulphonated phthalocyanine (AlSPc) for colonic PDT. The peak concentration of AISPc in the colon measured by alkali extraction occurred 1 h after i.v. injection. The cellular uptake demonstrated by laser fluorescence microscopy was greater in the mucosa than in the muscle. AlSPc was activated in the tissues by light from an argon ion pumped dye laser at 675nm. The laser power was set at lOOmW and the fibre placed touching the mucosa. In control animals no macroscopic damage was seen. Temperature measurement using a microthermocouple array showed no temperature rise during light exposure. The energy (fluence), dose of sensitiser and time from sensitisation to phototherapy were altered and the area of necrosis measured. The geometry of the colon made theoretical analysis of the correlation between laser energy and size of lesion difficult. However, following direct measurement of the relative light intensity (fluence rate) in the colon we were able to confirm that there was a threshold fluence for colonic necrosis. The area of photodynamic damage seen 72h after phototherapy fell with the fall in tissue concentration of AISPc from I h to 1 month after i.v. injection. However, maximum tissue necrosis occurred when treatment was performed immediately after i.v. injection. In this situation, intense vascular spasm was seen and any light transmitted through the colon which fell on the small bowel mesentery caused a lethal ischaemic necrosis.The initial histological changes after PDT were vascular, followed by full thickness necrosis at 72 h. Healing by regeneration was complete by 2-3 weeks. Despite full thickness necrosis there was no reduction in the colonic bursting pressure at any time. Colon treated by hyperthermia had a reduced bursting pressure. Specific collagen stains showed that PDT did not alter the submucosal collagen architecture whereas hyperthermia did.Photodynamic therapy (PDT) offers the potential of selectively destroying malignant tumours. Several photosensitising agents are retained longer in tumours and rapidly growing tissues than in the surrounding normal tissue. Illumination of the tumour with light of wavelengths absorbed by these agents results in tumour cell destruction (Doiron & Gomer, 1984). In spite of the potential of this technique there are certain disadvantages in the presently most widely used photosensitiser, haematoporphyrin derivative (HpD). It is a complex mixture of porphyrins whose composition varies with differing preparations and time in storage. Efforts have been directed at identifying the active component and it has been variously described as dihaematoporphyrin ether (Dougherty et al., 1984) or...

Local eradication of rat colon cancer with photodynamic therapy: correlation of distribution of photosensitiser with biological effects in normal and tumour tissue.

“…5 The nature of damage in tumours seen in this study was similar with an initial vascular dilatation, haemorrhage, and subsequent shutdown. Figure 5 shows a tumour 48 hours after photodynamic therapy.…”

Photodynamic therapy of the normal rat stomach: a comparative study between di-sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid

“…We have previously reported the efficacy of aluminium sulphonated phthalocyanine (AlSPc) as a photosensitiser in both normal tissue and tumours (Barr et al, 1987a;Tralau et al, 1987;Barr et al, 1990) as well as its advantages over haematoporphyrin derivative with respect to cutaneous phototoxicity (Tralau et al, 1989). We have further observed that PDT using AlSPc does not compromise the mechanical strength of the normal colon (Barr et al, 1987b).…”

Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model

“…These results show broad correlation with the corresponding mucosal fluorescence measurements from the CCD imaging studies with greatest damage also found at 4 h (mean diameter 9.1 ± 1.5 mm) with no visible necrosis at 24 h. The notable exception was at 30 min where considerable necrosis was seen (mean diameter 7.2 ± 1.0 mm) even though mucosal fluorescence was more than an order of magnitude lower than at 4 h. Histological examination was undertaken on all specimens showing macroscopic necrosis 72 h after laser treatment. At all treatment times after introduction of ALA, an acute inflammatory infiltrate, mainly comprising of monocytes and polymorphonuclear neutrocytes, was seen throughout all tis- Barr et al, 1987). It is reassuring that necrosis does not extend into the muscle layer, although there is evidence of an inflammatory infiltrate.…”