The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo

Leveckis, John; Brown, Nicola J.; Reed, Malcolm

doi:10.1038/bjc.1995.473

Cited by 26 publications

(17 citation statements)

References 31 publications

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“…This is in accordance with early studies and recent reports on vascular constriction in connection with PDT (Selman et al, 1984;Kessel, 1984;Van der Veen et al, 1994;Roberts et al, 1994;Leveckis et al, 1995). A sharply decreased blood flow was also noticed by a gross examination immediately after the irradiation, as the treated area became darker as a result of the treatment.…”

Section: Discussionsupporting

confidence: 92%

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Svanberg

Liu²,

Wang³

et al. 1996

Br J Cancer

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Summary The efficacy of photodynamic therapy (PDT) using 6-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour cells through the portal vein in rats. ALA at a dose of 60 mg kg-' b.w. was intravenously administered 60 min before PDT. PpIX accumulation in tumour, normal liver and abdominal wall muscle was detected by means of laser-induced fluorescence (LIF). Laser Doppler imaging (LDI) was used to determine changes in the superficial blood flow in connection with PDT. Histopathological examinations were performed to evaluate the PDT effects on the tumour and the surrounding liver tissue, including pathological features in the microvascular system. The accumulation of PpIX, as monitored by LIF, showed high fluorescence intensities at about 635 nm in both the hepatic tumour tissue and normal liver and low values in the abdominal wall. LDI demonstrated that the blood flow in the treated tumour and its surrounding normal liver tissue decreased immediately after the PDT, indicating an effect on the vascular system. A large number of thrombi in the irradiated tumour were found microscopically 3 h after the PDT. The tumour growth rate showed a marked decrease when evaluated 3 and 6 days after the treatment. These results show that the ALA-PDT is effective in the inhibition of growth of experimental hepatic tumours.

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Section: Discussionsupporting

confidence: 92%

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Svanberg

Liu²,

Wang³

et al. 1996

Br J Cancer

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“…Microvascular damage, which in some instances can even result in blood flow stasis, has frequently been seen following PDT (Reed et al, 1988;Fingar et al, 2000;Dolmans et al, 2002). Investigations of the effects of ALA-PDT on the microcirculation have shown decreases in perfusion in a number of experimental and human tumours (Roberts et al, 1994;Svanberg et al, 1996;Herman et al, 1999) and in normal tissue (Leveckis et al, 1995). However, in some tumour models, a lack of significant changes in blood flow has also been reported (Herman et al, 1999).…”

Section: Resultsmentioning

confidence: 99%

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

et al. 2003

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The possibility of enhancing aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) by simultaneous application of localised hyperthermia (HT) was evaluated. Treatments of rat DS-sarcomas included: (i) control, (ii) ALA administration (375 mg kg À1 , i.p.), no illumination, (iii) 'nonthermal' illumination, (iv) ALA-PDT: that is, ALA administration, 'nonthermal' illumination, (v) localised HT, 431C, 60 min (vi) ALA-PDT þ HT: ALA administration with full spectrum irradiation resulting in ALA-PDT and HT. Tumour volume was monitored for 90 days or until a target volume (3.5 ml) was reached. No differences were seen between the first three groups, with all tumours reaching the target volume by 8 -11 days. A total of 13 and 15% of tumours did not reach the target volume by day 90 following HT or ALA-PDT treatment, respectively. ALA-PDT þ HT showed the greatest antitumour effect (P ¼ 0.0001), with 61% of the tumours not reaching the target volume. Viability and in vitro growth were also assessed in cells from tumours excised after treatment. ALA-PDT þ HT reduced the fraction of viable tumour cells by 85%, and in vitro culture showed pronounced growth delay compared to control cells. These results demonstrate an enhanced antitumour effect upon ALA þ HT, which appears to involve direct cell toxicity rather than solely vascular damage.

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“…Exogenous 6-aminolaevulinic acid (ALA) is becoming widely used as an inducer of endogenous synthesis of protoporphyrin IX (PPIX), a photosensitizer used in photodynamic therapy (PDT) (Dilkes et al, 1995;Leveckis et al, 1995;Chang et al, 1996;Fromm et al, 1996). One of the limitations of this technique may be the extent to which ALA can enter the cell.…”

mentioning

confidence: 99%

Comparison of δ-aminolaevulinic acid and its methyl ester as an inducer of porphyrin synthesis in cultured cells

Washbrook

Riley²

1997

Br J Cancer

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Summary This study was carried out to test the hypothesis that induction of intracellular porphyrin synthesis by 6-aminolaevulinic acid (ALA) used to sensitize cells in photodynamic therapy would be more efficient if the ALA was used in an esterified form. Contrary to expectation, the generation of tetrapyrroles (TP) by cultured epithelial cells (CNCM-1-221) exposed to equimolar concentrations (0.6 mM) of ALA or its methyl ester (ALA-ME) showed that the mean total TP production rate during 6 h incubation in serum-free medium was 0.13 fmol cell-' h-1 for ALA-exposed cells compared with 0.04 fmol cell-1 h-1 for cells exposed to ALA-ME. Fluorescein diacetate uptake and conversion to fluorescein indicated intracellular non-specific esterase activity, implying that ALA-ME conversion to ALA can occur. Cells exposed to ALA-ME exhibited loss of a greater proportion of total tetrapyrroles in the form of extracellular protoporphyrin IX (PPIX; 22.8%) compared with 11.6% in ALA-treated cells with a corresponding reduction in cell-associated PPIX (P < 0.05). A variable initial elevation in haem levels in ALA-MEtreated cells was observed, but did not reach statistically significant levels.

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The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo

Cited by 26 publications

References 31 publications

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Photodynamic therapy using intravenous δ-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

Comparison of δ-aminolaevulinic acid and its methyl ester as an inducer of porphyrin synthesis in cultured cells

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