Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Milanesi, Carla; Zhou, Chen; Biolo, Roberta; Jori, G

doi:10.1038/bjc.1990.189

Cited by 60 publications

(22 citation statements)

References 16 publications

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“…The biodistribution and PDT efficacy of ZnPc have previously been studied extensively using standard liposomal preparations (Reddi et al, 1987Milanesi et al, 1990) and ZnPc encapsulated in a proprietary liposomal preparation has been proposed for clinical trials (Schieweck et al, 1994). Our tumour uptake and blood clearance data of the [65Zn]ZnPc in CRM-emulsions are similar to the earlier reported finding with liposomal ZnPc preparations (Reddi et al, 1987).…”

Section: Discussionsupporting

confidence: 84%

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

Boyle

Rousseau²,

Kudrevich³

et al. 1996

Br J Cancer

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Summary Hexadecafluorinated zinc phthalocyanine (ZnPcF,6), an analogue of zinc phthalocyanine (ZnPc) in which all hydrogen atoms have been substituted by fluorine, was prepared as a single isomeric product via the condensation of tetrafluorophthalonitrile with zinc acetate. Fluorination renders the ZnPc soluble in most common solvents. The photodynamic properties and pharmacokinetics of the ZnPcF,6 were evaluated in EMT-6 tumour-bearing Balb/c mice using 65Zn-radiolabelled analogues. Both dyes, administered i.v. at fLmol kg-' as Cremophor emulsions, revealed good tumour uptake [approximately 8-9 per cent of the injected dose per g tissue (%ID g-')] at 24 h post injection (p.i.), with the fluorinated dye reaching higher concentrations (approximately 11%ID g -') at 48 h p.i. and subsequently higher tumour -blood ratios due to rapid blood clearance. ZnPcF,6 at a dose of 5 pmol kg-' (4.3 mg kg-') induced complete tumour regression after phototherapy (24 h p.i., 650 -700 nm band, 360 J cm-2, 200 mW cm -'). At a dose of 2 fimol kg-' and phototherapy at 24 h p.i., the tumour volume doubling time increased to 11 days vs 6 days for the control tumours. A similar tumour growth delay was observed when phototherapy was conducted at 48 h or 72 h after dye injection implying that tumour response correlates with tumour dye concentrations rather than serum concentrations. As a result of its low solubility, the administered dose of ZnPc was limited to 1 fimol kg-' and at this drug level significant tumour response was only observed when the dye was solubilised as the pyridinium salt. Isolation of the neoplastic cells after in vivo dye administration and in vitro exposure to red light followed by a colony formation assay showed that the ZnPcF,6 exhibited a 1-2 order of magnitude higher potential for direct cell killing as compared with Photofrin and about a five times lower efficiency than ZnPc. However, all three photosensitisers induced complete occlusion of tumour vasculature immediately after PDT, suggesting that tumour regression mainly resulted from vascular stasis. The ZnPcF,6 offers several advantages over ZnPc for clinical applications, including improved solubility in most solvents, resulting in facilitated drug formation, favourable pharmacokinetics as well as the potential use in fluorine magnetic resonance (F-MR) imaging.

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Section: Discussionsupporting

confidence: 84%

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

Boyle

Rousseau²,

Kudrevich³

et al. 1996

Br J Cancer

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“…Interestingly, the amount of Zn-PC in the tumor decreases very slowly as a function of time following administration. Ultrastructural analysis of Zn-PC mediated photosensitization in this tumor model shows an early (3 h) component of photodamage to malignant cells (corresponding to mitochondria1 and endoplasmic reticulum injury) while capillary damage occurring later (15 h) (Milanesi et al, 1990). These results support the hypothesis that LDL plays a major role in the delivery of Zn-PC directly to tumor tissue.…”

Section: In Vivo Pharmacology and Toxicology Of Photosensitizerssupporting

confidence: 78%

PRECLINICAL EXAMINATION OF FIRST and SECOND GENERATION PHOTOSENSITIZERS USED IN PHOTODYNAMIC THERAPY

Gomer

1991

Photochem & Photobiology

329

142

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“…The destruction of a tumor cell and the resulting necrosis due to damage to the lysosome membrane causes the dissociation of a large amount of proteinase (29). According to this phenomenon, damage to the cell membrane causes failure of the arachidonic acid metabolism as well as blood vessel injury.…”

Section: Discussionmentioning

confidence: 99%

Combination treatment of Cetuximab and photodynamic therapy in SNU-1041 squamous cancer cell line

Kim

Hong²,

Boo³

et al. 2009

Oncol Rep

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Abstract. Cetuximab (Erbitux) has been highlighted for its anti-proliferative effects in solid tumors and it is currently used as an adjuvant modality with other anti-cancer treatments. Photodynamic therapy (PDT) is used widely in many specialties of medicine. This study evaluated the efficacy of a combination treatment of two modalities (Cetuximab, PDT) both in vivo and in vitro. The SNU-1041 cell line was used for both the in vitro and in vivo studies. The in vivo and in vitro experiments were each classified into four groups, control group, Cetuximab applied group, PDT applied group and combined modality group. A migration study was performed to determine the anti-migration effect of Cetuximab, and a MTT assay was performed to compare the anti-proliferative effect of the modalities in vitro. For the in vivo study, the cells were implanted into 5-week-old nude mice. The measured volume of the tumor for each group was compared as a function of time. In the migration study, the control group showed a longer migration length than the Cetuximab applied group. In the MTT assay, the combination modality group showed less survival than the uni-modality groups. The measured tumor size after treatment showed that the combination treatment was more effective than the single modalities. PDT and Cetuximab are treatment modalities that target different molecular pathways. A combination of these two treatment modalities was found to more effective than an individual treatment. However, further studies will be needed to determine the optimal dose of the photosensitizer and Cetuximab.

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Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Cited by 60 publications

References 16 publications

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

PRECLINICAL EXAMINATION OF FIRST and SECOND GENERATION PHOTOSENSITIZERS USED IN PHOTODYNAMIC THERAPY

Combination treatment of Cetuximab and photodynamic therapy in SNU-1041 squamous cancer cell line

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