Tumor Vascular Shutdown Following Photodynamic Therapy Based on Polyhematoporphyrin or 5-Aminolevulinic Acid

Roberts, Djh; Cairnduff, F; Driver, Ian D.; Dixon, B.; Brown, Sylvia T.

doi:10.3892/ijo.5.4.763

Cited by 31 publications

(33 citation statements)

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“…At both high and low fluence rates tumour pO2 dropped steadily with time after treatment (Table 2), consistent with our earlier reports of increasing tumour hypoxia after PDT (Henderson and Fingar, 1987) and studies by others (Roberts et al, 1994;Chen et al, 1996). Consistent with the above observations, no differences were found in tumour perfusion after high-or low-fluence-rate PDT.…”

Section: Discussionsupporting

confidence: 91%

“…Consistent with the above observations, no differences were found in tumour perfusion after high-or low-fluence-rate PDT. In both cases, tumour perfusion progressively decreased with time after treatment as has been described by others (Roberts et al, 1994;van Geel et al, 1994van Geel et al, , 1996. However, marked differences were found in cutaneous perfusion.…”

Section: Discussionsupporting

confidence: 80%

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Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Sitnik

Hampton²,

Henderson³

1998

Br J Cancer

248

204

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Summary It has been proposed that the generation of 102 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on P02, in the murine RIF tumour during and after PDT using 5 mg kg-' Photofrin and fluence rates of 30, 75 or 150 mW cm-2. Median P02 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour P02 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm-2) P02 recovered at the 30 mW cm-2 fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm-2 fluence rate (median P02 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm-2 median tumour P02 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm-2 at 30 mW cm-2 caused significantly (P= 0.0004) longer median tumour regrowth times than PDT at 150 mW cm-2, indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour P02, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 80%

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Sitnik

Hampton²,

Henderson³

1998

Br J Cancer

248

204

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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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“…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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Tumor Vascular Shutdown Following Photodynamic Therapy Based on Polyhematoporphyrin or 5-Aminolevulinic Acid

Cited by 31 publications

References 0 publications

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

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

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