Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval.

We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (P<0.05 compared to 1.5h and P<0.01 compared to 1h, 30 min and a single illumination). No relationship could be shown between the utilized PpIX fluorescence during the two-fold illumination and the PDT response. The rate of photobleaching was comparable for the first and the second light fraction and not dependent of the length of dark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.

[1]  O. Gederaas,et al.  The effect of brief illumination on intracellular free calcium concentration in cells with 5-aminolevulinic acid-induced protoporphyrin IX synthesis. , 1996, Scandinavian journal of clinical and laboratory investigation.

[2]  A. Curnow,et al.  Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes. , 2000, Journal of photochemistry and photobiology. B, Biology.

[3]  R. Rava,et al.  Analytical model for extracting intrinsic fluorescence in turbid media. , 1993, Applied optics.

[4]  T. Foster,et al.  Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. , 1995, Cancer research.

[5]  E. Hull,et al.  Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy , 1999, British Journal of Cancer.

[6]  H. S. de Bruijn,et al.  Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. , 1999, Cancer research.

[7]  T. Hasan,et al.  A theoretical study of light fractionation and dose-rate effects in photodynamic therapy. , 1997, Radiation research.

[8]  W. Star,et al.  In vivo fluorescence kinetics and photodynamic therapy using 5-aminolaevulinic acid-induced porphyrin: increased damage after multiple irradiations. , 1994, British Journal of Cancer.

[9]  M. Landthaler,et al.  Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo , 2003, British Journal of Cancer.

[10]  A. Curnow,et al.  Comparing and combining light dose fractionation and iron chelation to enhance experimental photodynamic therapy with aminolevulinic acid , 2006, Lasers in surgery and medicine.

[11]  Henricus J C M Sterenborg,et al.  Dose and Timing of the First Light Fraction in Two-fold Illumination Schemes for Topical ALA-mediated Photodynamic Therapy of Hairless Mouse Skin¶ , 2003, Photochemistry and photobiology.

[12]  Alison Curnow,et al.  Light Dose Fractionation to Enhance Photodynamic Therapy Using 5‐Aminolevulinic Acid in the Normal Rat Colon , 1999, Photochemistry and photobiology.

[13]  M. Olivo,et al.  Subcellular Localization of Photofrin and Aminolevulinic Acid and Photodynamic Cross‐Resistance in Vitro in Radiation‐Induced Fibrosarcoma Cells Sensitive or Resistant to Photofrin‐Mediated Photodynamic Therapy , 1997, Photochemistry and photobiology.

[14]  Stanley B. Brown,et al.  Fluorescence Photobleaching of ALA‐induced Protoporphyrin IX during Photodynamic Therapy of Normal Hairless Mouse Skin: The Effect of Light Dose and Irradiance and the Resulting Biological Effect , 1998, Photochemistry and photobiology.

[15]  K. Smetana,et al.  Mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by 5-aminolevulinic acid-based photodynamic therapy in HL60 leukemia cells. , 2003, Journal of photochemistry and photobiology. B, Biology.

[16]  H. S. de Bruijn,et al.  Evidence for a bystander role of neutrophils in the response to systemic 5‐aminolevulinic acid‐based photodynamic therapy , 2006, Photodermatology, photoimmunology & photomedicine.

[17]  Henricus J C M Sterenborg,et al.  Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic acid photodynamic therapy. , 2006, The Journal of investigative dermatology.

[18]  M G Nichols,et al.  Quantitative broadband near-infrared spectroscopy of tissue-simulating phantoms containing erythrocytes. , 1998, Physics in medicine and biology.

[19]  W. Star,et al.  Topical 5-aminolaevulinic acid mediated photodynamic therapy of superficial basal cell carcinoma using two light fractions with a two-hour interval: Long-term follow-up , 2006 .

[20]  T. Foster,et al.  Oxygen consumption and diffusion effects in photodynamic therapy. , 1991, Radiation research.

[21]  G. Buonaccorsi,et al.  Enhancement of photodynamic therapy with 5-aminolaevulinic acid-induced porphyrin photosensitisation in normal rat colon by threshold and light fractionation studies. , 1995, British Journal of Cancer.

[22]  H. S. de Bruijn,et al.  Topical 5-Aminolevulinic Acid-photodynamic Therapy of Hairless Mouse Skin Using Two-fold Illumination Schemes: PpIX Fluorescence Kinetics, Photobleaching and Biological Effect†¶ , 2000, Photochemistry and photobiology.

[23]  Stanley B. Brown,et al.  Protoporphyrin IX Fluorescence Photobleaching during ALA‐Mediated Photodynamic Therapy of UVB‐Induced Tumors in Hairless Mouse Skin , 1999, Photochemistry and photobiology.

[24]  W. Star,et al.  Photodynamic Effectiveness and Vasoconstriction in Hairless Mouse Skin after Topical 5‐Aminolevulinic Acid and Single‐ or Two‐fold Illumination , 1999, Photochemistry and photobiology.