&lt;title&gt;CGP 55 847, liposome-delivered zinc(II)-phthalocyanine as a phototherapeutic agent for tumors&lt;/title&gt;

Schieweck, K.; Capraro, Hans‐Georg; Isele, Ute; Hoogevest, Peter van; Ochsner, Martin; Maurer, Tobias; Batt, Ernst

doi:10.1117/12.168675

Cited by 24 publications

(18 citation statements)

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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%

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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%

“…The material is highly insoluble in most common solvents and a proprietary liposomal formulation has been advanced for clinical trials (Schieweck et al, 1994). To overcome such solubility problems we proposed the fluorinated analogue of ZnPc as a sensitiser for PDT (Boyle and van Lier, 1991).…”

mentioning

confidence: 99%

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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“…Thus, the in vivo PDT effect following ZnPc-BSA administration is likely to involve the same mechanism as that observed with similar dyes delivered via liposomal preparations . Compared with the latter, ZnPc loading on albumin is a relatively simple procedure (Schieweck et al, 1994). To avoid antigenecity problems, it is evident that the same procedure can be used with human albumin preparations.…”

Section: Discussionmentioning

confidence: 99%

“…Among the non-substituted Pcs, the zinc complex (ZnPc) has been studied in great detail (Ginevra et al, 1990;Reddi et al, 1990). Owing to its extreme insolubility in most common solvents, ZnPc needs to be incorporated in liposomes, and a proprietary formulation has been proposed for clinical use (Schieweck et al, 1994).…”

mentioning

confidence: 99%

Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in solid tumour models

Larroque

Pèlegrin²,

Lier³

1996

Br J Cancer

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Summary Zinc phthalocyanine (ZnPc) is a second-generation photosensitiser for the photodynamic therapy (PDT) of cancer. Unsubstituted ZnPc is, however, highly insoluble in most common solvents, and for clinical applications the material needs to be incorporated in liposomes. We report a simple, alternative procedure to formulate ZnPc through non-covalent binding to bovine serum albumin (BSA). Intravenous administration of ZnPc-BSA preparations, at a molar ratio of 11: 1 and at a ZnPc dose equivalent to 0.5 mol kg-, to tumourbearing mice followed 24 h later by PDT was shown to provide tumour control in two different models, the EMT-6 tumour in Balb/c mice and the human colon T380 carcinoma in nude mice. Analysis of serum fractions from treated animals showed that ZnPc readily redistributes over the serum high-density lipoprotein (HDL) fraction. We also demonstrated the absence of hepatic toxicity of the ZnPc-BSA preparation by monitoring the hepatic cytochrome P450 activiy in treated animals and the viability of human cultured hepatocytes.

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“…ZnPc (purity Ͼ99%) was supplied by Ciba-Geigy (Basel, Switzerland) as a freeze-dried liposomal formulation (Schieweck et al, 1994;Valduga et al, 1996). The ZnPcTS was a gift from J.E.…”

Section: Chemicalsmentioning

confidence: 99%

Photosensitization of cells with different metastatic potentials by liposome-delivered Zn(II)-phthalocyanine

et al. 1998

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The phototoxicity of liposome‐incorporated Zn(II)‐phthalocyanine (ZnPc) and its water‐soluble tetrasulphonated derivative (ZnPcTS) was studied in the tumorigenic but nonmetastatic (RE4) and the highly metastatic (4R) transformed rat embryo fibroblasts. Upon irradiation with 585–605 nm light in the presence of ZnPc, the cell survival drastically decreased, while it was unaffected by ZnPcTS. Enzymatic assays showed that ZnPc induced about a 60% decrease in the activity of the mitochondrial enzymes NADH and succinate dehydrogenase after 3 min of irradiation, while no significant reduction in the activity of lactate dehydrogenase and lysosomal N‐acetyl‐β‐glucosaminidase was observed. The transport of thymidine, deoxyglucose and α‐aminoisobutyric acid through the plasma membrane was strongly inhibited after irradiation. Similarly, the intracellular ATP content was significantly reduced. The reduction of DNA biosynthesis showed a time dependence quite similar to the photo‐induced decrease in cell survival. No repair of cellular functions affected by ZnPc was observed in the 2 cell lines. These results indicate that, under our experimental conditions, hydrophobic ZnPc exerts its cytotoxic activity mainly by impairing those functions localized in the plasma membrane of the cells. Int. J. Cancer 75:412–417, 1998. © 1998 Wiley‐Liss, Inc.

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<title>CGP 55 847, liposome-delivered zinc(II)-phthalocyanine as a phototherapeutic agent for tumors</title>

Cited by 24 publications

References 0 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

Serum albumin as a vehicle for zinc phthalocyanine: photodynamic activities in solid tumour models

Photosensitization of cells with different metastatic potentials by liposome-delivered Zn(II)-phthalocyanine

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