Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer

Chan, Wai-Shun; Svensen, R.; Phillips, David; Hart, Ian R.

doi:10.1038/bjc.1986.43

Cited by 117 publications

(57 citation statements)

References 22 publications

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“…Therefore we have been investigating a new group of sensitisers, the phthalocyanines. Chloro aluminium sulphonated phthalocyanine (AlSPc) has been shown to be effective at sensitising the destruction of cells in culture Chan et al, 1986). We have shown that AlSPc is a more effective sensitiser than HpD for the treatment of the liver and a subcutaneous transplanted fibrosarcoma in the rat Tralau et al, 1987).…”

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confidence: 86%

Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation

Barr

Tralau²,

MacRobert³

et al. 1987

Br J Cancer

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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...

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confidence: 86%

Photodynamic therapy in the normal rat colon with phthalocyanine sensitisation

Barr

Tralau²,

MacRobert³

et al. 1987

Br J Cancer

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“…The emission spectra of this source has been documented elsewhere (Chan et al, 1986 The procedure used to establish AlSnPc-mediated cytotoxicity against WiDr cultures was similar to that described previously for PII (West, 1989 (Chan et al, 1990). …”

Section: Tumour Cellsmentioning

confidence: 99%

“…Generally, the active MPc contain central diamagnetic metal ions, such as aluminium, gallium, tin and zinc (Brasseur et al, 1985;Ben-Hur & Rosenthal, 1986;Brasseur et al, 1987;Chan et al, 1987aChan et al, , 1988Brasseur et al, 1988;Paquette et al, 1988) while sulphonation of the benzene rings of the macrocycle leads to solubility in water which facilitates administration to animals. One such compound, AlSPc, has been shown by ourselves (Chan et al, 1986(Chan et al, , 1988 and others (Sandeman et al, 1987;Tralau et al, 1987a;Nelson et al, 1988) to be a particularly promising agent for PDT. This substance possesses good tumour-localising capacity (Tralau et al, 1987a(Tralau et al, , 1987bChan et al, 1988Chan et al, , 1989 and causes substantial damage to a range of tumours of diverse histological origin (Sandeman et al, 1987;Tralau et al, 1987a;Chan et al, 1988;Nelson et al, 1988) with prolongation of survival times in treated animals (Chan et al, 1987b).…”

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confidence: 99%

“…Though AlSPc may induce a mild immunosuppression in mice it produces much less skin photosensitivity than occurs subsequent to HpD or PII administration which is the current clinical regimen for PDT (Tralau et al, 1989). AlSPc, as originally used by us (Chan et al, 1986) of species with varying degrees of sulphonation. The uptake and distribution of AlS,Pc by tumour cells both in vitro and in vivo was found to be affected quite profoundly by the degree of sulphonation (Chan et al, 1990).…”

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confidence: 99%

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Photocytotoxic efficacy of sulphonated species of aluminium phthalocyanine against cell monolayers, multicellular spheroids and in vivo tumours

Chan¹,

West²,

Moore³

et al. 1991

Br J Cancer

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“…ALSPc has the advantage that it is easily synthetised in reproducible form (a solution containing an average of three sulphonic acid groups per molecule). It is an effective photosensitiser both in vitro and in vivo and it has a single strong absorption peak in the visible spectrum at 675 nm (Chan et al, 1986). Outbred mice, weighing between 20-30 g were used for the normal studies and results compared with studies on the VMDk murine glioma model.…”

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confidence: 99%