CGP 55398, A LIPOSOMAL GE(IV) PHTHALOCYANINE BEARING 2 AXIALLY LIGATED CHOLESTEROL MOIETIES - A NEW POTENTIAL AGENT FOR PHOTODYNAMIC THERAPY OF TUMORS

Ge(IV) phthalocyanine (GePc) with two axially ligated cholesterol moie ties was prepared by chemical synthesis and incorporated in a monomeri c state into small unilamellar liposomes (CGP 55398). Upon photoexcita tion with light wavelengths around its intense absorption peak at 680 nm, GePc shows an efficient photosensitising activity towards biologic al substrates through a mechanism which largely involves the intermedi acy of singlet oxygen. GePc injected systemically into mice bearing an intramuscularly implanted MS-2 fibrosarcoma is quantitatively transfe rred to serum lipoproteins and localises in the tumour tissue with goo d efficiency: at 24 h post injection the GePc content in the tumour is 0.74 and 1.87 mu g per g of tissue with a tumour/peritumoral ratio of 4.35 and 5.67 for injected doses of 0.76 and 1.52 mg kg(-1) respectiv ely. At this time the red-light irradiation of the GePc-loaded fibrosa rcoma causes a fast and massive tumour necrosis involving both maligna nt cells and blood vessels.