Comparison of Distribution and Photodynamic Effects of Di‐ and Tetra‐sulphonated Aluminium Phthalocyanines in Normal Rat Colon

Abstract— —We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AlSPc). In that study, the AlSPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di‐ and tetra‐sulphonates (AlS 2 Pc and AlS 4 Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AlS 2 Pc in colon fell off more rapidly with time than AlS 4 Pc. Differences were noted in the microscopic distribution of these compounds, with the di‐sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra‐sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra‐sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AlS 2 Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 μmol/kg. With AlS 4 Pc (5.65 μmol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks. It is proposed that differences between AlS 2 Pc and AlS 4 Pc with respect to pharmacokinetics, microscopic distribution and qualitative (related to the timing) and quantitative differences in photodynamic effects in normal rat colon are related to physico‐chemical characteristics of the phthalocyanines used, particularly lipid solubility. Similar studies are now required on tumour bearing animals.