Abstract
Four novel zinc (II)-substituted phthalocyanines, varying in charge and hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic therapy. Two rat tumours with differing vascularity were used: a mammary carcinoma (LMC1) and a fibrosarcoma (LSBD1), with vascular components six times higher in the latter (10.8%+/-1.5) than in the former (1.8%+/-1.4). Each sensitizer was assessed for tumour response relative to normal tissue damage, and optimum doses were selected for further study, ranging from 0.5 to 20 mg kg(-1). Interstitial illumination of the tumours was carried out using a 200-microm-core optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm, depending on the sensitizer. Light doses of between 200 and 600 J were delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depending on sensitizer and type of tumour, with the most potent photosensitizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an infarct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cell damage could not be ruled out.
Highlights
We have developed a series of zinc phthalocyanines
We have demonstrated that the rate at which the light was delivered, i.e. 100 mW using the 0.5-cm diffusing tip fibre, produces no hyperthermic effects (C Lowdell and B Dixon, personal communication)
The pattern of Photodynamic therapy (PDT) response with ZnTCPc, zinc phthalocyanine tetrasulphonic acid tetra-sodium salt (ZnTSPc) and ZnPPc was similar for both the tumour models
Summary
Each spontaneous tumour was transplanted and used in their strain of origin. The first was a poorly differentiated fibrosarcoma (LSBD,) implanted subcutaneously, as a 2 mm fragment, in the right flank of female BDIX rats weighing between 180 and 250 kg (Gilson, 1990). The second was a poorly differentiated mammary carcinoma (LMCI) implanted as a 2-mm pellet of minced tumour. 966 JE Cruse-Sawyer et al Sensitizer xmax 6max Xmax e,f,, k (nm) (I mol-' cm-') (nm) (I mol-' cm-') (n-octanoV (DMFb) (DMFb) (MEMa) (MEM') water). AMinimal essential medium (MEM) containing 10% calf serum at pH 7.4; bDimethyl formanide x N x N Zn )X -' < X -...\ ZnTCPc ZnTSAPc 680 5.3 x 104 636 2.35 x 104 5 x 10-2 673 1.46 x 105 626 4.28 x 104 2 x 10-3 670 1.12 x 105 629 3.90 x 104 5 x 10-2 672 1.42 x 105 632 2.22 x 104 2 x 10 4 672 2.22 x 104
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