PHARMACOKINETIC AND PHOTOTHERAPEUTIC PROPERTIES OF AXIALLY SUBSTITUTED V)-TETRADIBENZOBARRELENO-OCTABUTOXYPHTHALOCYANINES

Three V)-tetradibenzobarreleno-octabutoxyphthalocyanines (TDiBOPcs) be aring different axial ligands on the metal ion were studied for their tumour-localizing and-photosensitizing properties after i.v. injection via a Cremophor emulsion (0.35 mu mol kg(-1) b.w.) to Balb/c mice bea ring an intramuscularly implanted MS-2 fibrosarcoma. In all cases, the maximum tumour accumulation of the photosensitizer (0.8-1.9 nmol g(-1 ) of tissue) was found at 24 h after injection, The efficiency and sel ectivity of tumour targeting appeared to be dependent on the nature of the axial ligands: optimal values of these parameters were obtained i n the case of the bis(trihexyl-siloxy)-substituted Si(IV)-TDiBOPc, whi ch gave a 7-9 tumour/muscle ratio of phthalocyanine concentration at 2 4-48 h after injection. The extent of tumour response to PDT treatment was correlated with the concentration of the photosensitizer in the t umour tissue: upon 740 nm irradiation (180 mW cm(-2) 200 J cm(-2)) at 48 h after injection of 0.35 mu mol kg(-1) of Si(IV)-TDiBOPc-C6H13, th e tumour growth exhibited a delay of about 7 days. (C) 1997 Elsevier S cience S.A.