Protoporphyrin IX Fluorescence Photobleaching and the Response of Rat Barrett's Esophagus Following 5-aminolevulinic Acid Photodynamic Therapy

Abstract Barrett's esophagus (BE) can experimentally be treated with 5-aminolevulinic acid–based photodynamic therapy (ALA-PDT), in which ALA, the precursor of the endogenous photosensitizer protoporphyrin IX (PpIX) and subsequent irradiation with laser light are applied to destroy the (pre)malignant tissue. Accurate dosimetry is critical for successful ALA-PDT. Here, in vivo dosimetry and kinetics of PpIX fluorescence photobleaching were studied in a rat model of BE. The fluence and fluence rate were standardized in vivo and PpIX fluorescence was measured simultaneously at the esophageal wall during ALA-PDT and plotted against the delivered fluence rather than time. Rats with BE were administered 200 mg kg−1 ALA (n = 17) or served as control (n = 4). Animals were irradiated with 633 nm laser light at a measured fluence rate of 75 mW cm−2 and a fluence of 54 J cm−2. Large differences were observed in the kinetics of PpIX fluorescence photobleaching in different animals. High PpIX fluorescence photobleaching rates corresponded with tissue ablation, whereas low rates corresponded with no damage to the epithelium. Attempts to influence tissue oxygenation by varying balloon pressure and ventilation were shown not to be directly responsible for the differences in effect. In conclusion, in vivo dosimetry is feasible in heterogeneous conditions such as BE, and PpIX fluorescence photobleaching is useful to predict the tissue response to ALA-PDT.

[1]  P. Siersema Photodynamic therapy for Barrett's esophagus: not yet ready for the premier league of endoscopic interventions. , 2005, Gastrointestinal endoscopy.

[2]  Michael S Patterson,et al.  Imaging of Photodynamically Generated Singlet Oxygen Luminescence In Vivo¶ , 2005, Photochemistry and photobiology.

[3]  M S Patterson,et al.  Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid , 2005, British Journal of Cancer.

[4]  E. Kuipers,et al.  Molecular evaluation of ablative therapy of Barrett's oesophagus , 2005, The Journal of pathology.

[5]  H. S. de Bruijn,et al.  Monitoring In Situ Dosimetry and Protoporphyrin IX Fluorescence Photobleaching in the Normal Rat Esophagus During 5‐Aminolevulinic Acid Photodynamic Therapy ¶ , 2003, Photochemistry and photobiology.

[6]  H. S. de Bruijn,et al.  Monitoring In Situ Dosimetry and Protoporphyrin IX Fluorescence Photobleaching in the Normal Rat Esophagus During 5-Aminolevulinic Acid Photodynamic Therapy¶ , 2003 .

[7]  Henricus J C M Sterenborg,et al.  In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5‐aminolevulinic acid , 2002, Lasers in surgery and medicine.

[8]  T. Foster,et al.  Effect of Irradiation Fluence Rate on the Efficacy of Photodynamic Therapy and Tumor Oxygenation in Meta-Tetra (Hydroxyphenyl) Chlorin (mTHPC)-Sensitized HT29 Xenografts in Nude Mice1 , 2002, Radiation research.

[9]  L. Gossner,et al.  Photodynamic therapy of human Barrett's cancer using 5-aminolaevulinic acid-induced protoporphyrin IX: an in-vivo dosimetry study in athymic nude mice , 2002, European journal of gastroenterology & hepatology.

[10]  Thomas H. Foster,et al.  In Vivo mTHPC Photobleaching in Normal Rat Skin Exhibits Unique Irradiance-dependent Features¶ , 2002, Photochemistry and photobiology.

[11]  P Baas,et al.  Wedge-shaped applicator for additional light delivery and dosimetry in the diaphragmal sinus during photodynamic therapy for malignant pleural mesothelioma. , 2001, Physics in medicine and biology.

[12]  A. Sonnenberg,et al.  Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia. , 2001, Gastroenterology.

[13]  K. Badizadegan,et al.  Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus. , 2001, Gastroenterology.

[14]  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.

[15]  H. J. van Staveren,et al.  Photodynamic therapy for esophageal lesions: selectivity depends on wavelength, power, and light dose. , 1999, The Annals of thoracic surgery.

[16]  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.

[17]  A B Houtsmuller,et al.  5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. , 1998, Journal of photochemistry and photobiology. B, Biology.

[18]  T. Foster,et al.  Singlet Oxygen‐Versus Nonsinglet Oxygen‐Mediated Mechanisms of Sensitizer Photobleaching and Their Effects on Photodynamic Dosimetry , 1998, Photochemistry and photobiology.

[19]  B. Henderson,et al.  Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. , 1998, British Journal of Cancer.

[20]  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.

[21]  H. Barr,et al.  Eradication of high-grade dysplasia in columnar-lined (Barrett's) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX , 1996, The Lancet.

[22]  W. Star,et al.  Calibration of isotropic light dosimetry probes based on scattering bulbs in clear media. , 1996, Physics in medicine and biology.

[23]  H. J. van Staveren,et al.  Integrating sphere effect in whole-bladder wall photodynamic therapy: III. Fluence multiplication, optical penetration and light distribution with an eccentric source for human bladder optical properties. , 1996, Physics in medicine and biology.

[24]  K König,et al.  In vivo photoproduct formation during PDT with ALA-induced endogenous porphyrins. , 1993, Journal of photochemistry and photobiology. B, Biology.

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

[26]  R. Lambert,et al.  Esophagitis produced by reflux of duodenal contents in rats , 1962, The American Journal of Digestive Diseases.

[27]  E. Hull,et al.  Porphyrin Bleaching and PDT-induced Spectral Changes are Irradiance Dependent in ALA-sensitized Normal Rat Skin In Vivo¶ , 2001, Photochemistry and photobiology.

[28]  R. Anderson,et al.  Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. , 1997, The Journal of investigative dermatology.

[29]  M. Keijzer,et al.  Integrating sphere effect in whole-bladder-wall photodynamic therapy: III. Fluence multiplication, optical penetration and light distribution with an eccentric source for human bladder optical properties , 1996 .

[30]  W. Star,et al.  The relationship between integrating sphere and diffusion theory calculations of fluence rate at the wall of a spherical cavity. , 1995, Physics in medicine and biology.