Phthalocyanines as Photodynamic Sensitizers*

Rosenthal, I.

doi:10.1111/j.1751-1097.1991.tb09900.x

Cited by 508 publications

(139 citation statements)

References 85 publications

(37 reference statements)

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“…It has been shown that the degree of sulphonation of AlPcS,s could significantly affect the distnrbution and the PDT effect of the dyes in some tumour and normal tissues of mice (Chan et al. 1990. 1991: Peng et al.…”

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confidence: 99%

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Peng

Moan²

1995

Br J Cancer

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Summan-A chemical extraction assax-and fluorescence microscopi incorporating a light-sensitive thermoelectnically cooled charge-coupled device (CCD) camera was used to study the kinetics of uptake. retention and localisation of disulphonated aluminium phthalocyanine (AIPcS-) and tetrasulphonated aluminium phthalocvanine (AlPcS4) at different time inten-als after an i.p. injection at a dose of 10 mg kg`body w-eight (b.Ax in tumour and surrounding normal skin and muscle of female C-D F, mice bearing CaD2 mammary carcinoma. Moreover. the photodymamic effect on the tumour and normal skin using sulphonated aluminium phthalocvanines (AIPcS,. AIPcS:. AlPcS4) and Photofrin was compared w-ith respect to dye, dve dose and time interval betu-een dve administration and light exposure. The maximal concentrations of AlPcS in the tumour tissue w-ere reached 2-24 h after injection of the dve. while the amounts of AIPcS4 peaked 1-2 h after the dve administration. AlPcS, was simultaneouslv localised in the interstitium and in the neoplastic cells of the tumour. uhereas AlPcS4 appeared to localise only in the stroma of the tumour. The photodynamic efficiency (light A-as applied 24 h after dye injection at a dose of 10 mg kg-' b.wu. of the tumours u-as found to decrease in the folloWing order: AlPcS > AIPcS4> Photofrin > AlPcSl. Furthermore. photodynamic efficacyv was strongly dependent upon dye doses and time intervals betw-een dye administration and light exposure: the higher the dose. the higher the photodynamic efficiency. The most efficient photodynamic therapy (PDT) of the tumour u-as reached (day 20 tumour-free) when light exposure took place 2 h after injection of AlPcS, (10 mg k-.) A dual intratumoral localisation pattern of the dye. as found for AlPcS:. seems desirable to obtain a high photodynamic efficiency. The kinetic patterns of uptake. retention and localisation of AlPcS, and AIPcS4 are roughly correlated w-ith their photodynamic effect on the tumour and normal skin.

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Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Peng

Moan²

1995

Br J Cancer

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“…Porphyrin derivatives are the most commonly administered photosensitizers. Modifications to the porphyrin structure have produced the so-called second-generation photosensitizers, including the phthalocyanines (Ben-Hur and Rosenthal, 1985;Rosenthal, 1991) and chlorins (Gomer, 1991) with TTR values ranging from 1:1 to 5:1 (Pass, 1993). Mesotetra(hydroxyphenyl)chlorin (m-THPC) is a chlorin photosensitizer with promising properties.…”

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Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC

et al. 1999

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Summary Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEGm-THPC at dosages of 0.3, 3.0 and 30 mg kg -1 body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm -1 diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg -1 body weight and an optical dose of 900 J cm -1 diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose-response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg -1 and 11 mm using 3 mg kg -1 photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm -1 diffuser-length for 30 mg kg -1 and between 300 and 500 J cm -1 for 3 mg kg -1 PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg -1 photosensitizer was activated with optical doses of 700 J cm -1 or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 ± 4.5 days compared to 38.4 ± 3.8 days and 40.0 ± 3.6 days for rats treated with 3 mg kg -1 or 9 mg kg -1 PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively.

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“…Phthalocyanines (Pcs) are among the various classes of dyes that have been proposed as sensitisers to supersede haematoporphyrin derivative (Photofrin II), currently used for clinical photodynamic therapy (PDT) of cancer (van Lier, 1990;Rosenthal, 1991). This is due to the superior molar absorptivity of these compounds (a> I05 M-1 cm-' when fully monomerised), at wavelengths permitting greater penetration of light in normal tissues (typically 670-680 nm), when compared with Photofrin (e 10' M-1cm-1 at 630 nm).…”

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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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Phthalocyanines as Photodynamic Sensitizers*

Cited by 508 publications

References 85 publications

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC

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

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