title: Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin.
abstract: Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS(2a)). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS(2a) fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg(-1) AlPcS(2a), and 6 h after direct intratumour injection of 50 microg gelonin (PCI) or a similar volume of phosphate-buffered saline (PDT controls), tumour-bearing animals were exposed to red light (150 J cm(-2)). Complete response was observed for more than 100 days in 50% of the PCI tumours but only 10% of the PDT tumours (P<0.01). In tumours examined histologically 4 days after light delivery, the depth of necrosis was 3-4 mm after PDT, but 7 mm after PCI. The deeper effect after PCI demonstrates that the light fluence needed to kill tumour is less than with PDT. We conclude that PCI with gelonin can markedly enhance the effect of PDT on this type of tumour and may have a role clinically as an adjunct to surgery to control localised disease.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. adietze@online.no
authors.forename: A
authors.initials: A
authors.lastname: Dietze
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
authors.forename: P K
authors.initials: PK
authors.lastname: Selbo
authors.forename: O
authors.initials: O
authors.lastname: Kaalhus
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Bown
authors.forename: K
authors.initials: K
authors.lastname: Berg
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology*; D022162:Cytoplasmic Vesicles; D004195:Disease Models, Animal; D006207:Half-Life; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy* / Q000662:veterinary; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007263:Infusions, Parenteral; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D010940:Plant Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C064331:aluminum phthalocyanine disulfonate; C025674:GEL protein, Gelonium multiflorum