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Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin.

Dietze A, Peng Q, Selbo PK, Kaalhus O, Müller C, Bown S, Berg K - Br. J. Cancer (2005)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. adietze@online.no

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.

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Photomicrographs of tumours 4 days after treatment. Areas of complete necrosis were clearly demarcated from adjacent viable tissue (arrows). (A) Tumour treated with PCI. (B) tumour treated with PDT.
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fig6: Photomicrographs of tumours 4 days after treatment. Areas of complete necrosis were clearly demarcated from adjacent viable tissue (arrows). (A) Tumour treated with PCI. (B) tumour treated with PDT.

Mentions: Histological examination of the central area of tumours 4 days after treatment showed that in the PDT group, a mean of 25% of the tumour was viable compared with 2.5% in the PCI group (P<0.001) (Figure 6). Measured from the surface of the skin, the PDT effect was typically 3–4 mm deep compared with 6–7 mm (and usually reaching the bottom of the tumour mass) for the PCI group (Figure 6). Intratumour injection of gelonin or PBS with or without light application induced a small amount of necrosis in the centre of the tumour, presumably due to a local pressure effect. However, this had no influence on the survival curve (Figure 5) or the tumour growth (data not shown).


Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin.

Dietze A, Peng Q, Selbo PK, Kaalhus O, Müller C, Bown S, Berg K - Br. J. Cancer (2005)

Photomicrographs of tumours 4 days after treatment. Areas of complete necrosis were clearly demarcated from adjacent viable tissue (arrows). (A) Tumour treated with PCI. (B) tumour treated with PDT.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361782&req=5

fig6: Photomicrographs of tumours 4 days after treatment. Areas of complete necrosis were clearly demarcated from adjacent viable tissue (arrows). (A) Tumour treated with PCI. (B) tumour treated with PDT.
Mentions: Histological examination of the central area of tumours 4 days after treatment showed that in the PDT group, a mean of 25% of the tumour was viable compared with 2.5% in the PCI group (P<0.001) (Figure 6). Measured from the surface of the skin, the PDT effect was typically 3–4 mm deep compared with 6–7 mm (and usually reaching the bottom of the tumour mass) for the PCI group (Figure 6). Intratumour injection of gelonin or PBS with or without light application induced a small amount of necrosis in the centre of the tumour, presumably due to a local pressure effect. However, this had no influence on the survival curve (Figure 5) or the tumour growth (data not shown).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway. adietze@online.no

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.

Show MeSH
Related in: MedlinePlus