TUMOR-LOCALIZING AND TUMOR-PHOTOSENSITIZING PROPERTIES OF A NOVEL ZINC(II) OCTADECYLPHTHALOCYANINE

1,4,8,11,15,18,22,25-Octadecylphthalocyaninato zinc(II), ZnODPc, incor porated into a Cremophor emulsion, was assayed for its pharmacokinetic and phototherapeutic properties in Balb/c mice bearing an intramuscul arly transplanted MS-2 fibrosarcoma. The phthalocyanine was injected i ntravenously (i.v.) in three doses. i.e. 1.46, 0.73 and 0.37 mu mol kg (-1) body weight. In all cases, the octadecyl-substituted phthalocyani ne showed an unusually high affinity for serum low-density lipoprotein s (LDLs) and a high efficiency and selectivity of tumour targeting: th e maximum accumulation in the tumour occurred at 24 h after injection, whereas no detectable amount of phthalocyanine was recovered from the muscle, i.e. the peritumoral tissue, between 1 h and 1 week after inj ection. At the same time, low amounts of phthalocyanine were recovered from skin and then only at short times after injection, with skin pho tosensitivity rapidly disappearing and the phthalocyanine present in t he serum only. Tumour photosensitisation studies were carried out at 2 4 h after administration of 1.46 mu mol kg(-1) ZnODPc and showed that this phthalocyanine has a very high phototherapeutic efficiency; this is probably a consequence of the multiple mechanisms by which the phth alocyanine induces tumour damage, involving both direct modification o f malignant cells and impairment of blood flow, as well as the alterat ion of a variety of subcellular components, such as mitochondria, the rough endoplasmic reticulum, the perinuclear membrane and, occasionall y, cell nuclei. Tumour necrosis appears to he the consequence of both random cell death and apoptosis.