The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines.
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.
Cruse-Sawyer
J E
JE
Research School of Medicine, Department of Biochemistry and Molecular Biology, Centre for Photobiology and Photodynamic Therapy, The University of Leeds, UK.
Griffiths
J
J
Dixon
B
B
Brown
S B
SB
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use*; D054833:Isoindoles; D008027:Light; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D015032:Zinc; C013647:phthalocyanine