C. Ometto et al., TUMOR-LOCALIZING AND TUMOR-PHOTOSENSITIZING PROPERTIES OF A NOVEL ZINC(II) OCTADECYLPHTHALOCYANINE, British Journal of Cancer, 74(12), 1996, pp. 1891-1899
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.