Laurie Guyon1, Marie-Odile Farine2, Jean Claude Lesage3, Anne-Marie Gevaert2, Sylvie Simonin4, Caroline Schmitt4, Pierre Collinet1, Serge Mordon5. 1. Department of Gynaecology and Obstetrics, Lille University Hospital, Lille, France; INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France. 2. Centre de biologie-pathologie, Lille University Hospital, Lille, France. 3. INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France. 4. Centre Français des Porphyries, Hôpital Louis Mourier, Colombes, France; INSERM U773, Paris Diderot University, Paris, France. 5. INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France; GDR 3049 Médicaments Photoactivables - Photochimiothérapie (PHOTOMED), France. Electronic address: serge.mordon@inserm.fr.
Abstract
CONTEXT: While photodynamic therapy (PDT) is a promising treatment for peritoneal carcinomatosis, its use is often limited because of the toxicity of photosensitizers. In this study, safety of PDT with hexaminoevulinate (HAL), a second generation photosensitizer, is assessed. METHODS: PDT of the peritoneal cavity was performed in a rat model of peritoneal carcinomatosis. Rats were treated according to different protocols: with full or half HAL dose, after intraperitoneal or oral administration of HAL, 4 or 8h after its injection, using red or green light, after protection of the liver or cooling of the abdominal wall. Toxicity was assessed by blood tests quantifying hematocrit, liver and muscular enzymes and by pathological examination of abdominal and intrathoracic organs after treatment. The results were analyzed in the light of quantification of fluorescence and protoporphyrin IX (PPIX) content of the same organs. RESULTS: PDT with HAL induced rhabdomyolysis, intestinal necrosis and liver function test anomalies, leading to death in 2 out of 34 rats. The liver and the intestine contained high levels of PPIX (3-5 times more than tumor nodules). CONCLUSION: HAL PDT lacked specificity. However, the strategy associating diagnosis, treatment and evaluation of the results in one single procedure was effective and should be tested with other photosensitizers.
CONTEXT: While photodynamic therapy (PDT) is a promising treatment for peritoneal carcinomatosis, its use is often limited because of the toxicity of photosensitizers. In this study, safety of PDT with hexaminoevulinate (HAL), a second generation photosensitizer, is assessed. METHODS: PDT of the peritoneal cavity was performed in a rat model of peritoneal carcinomatosis. Rats were treated according to different protocols: with full or half HAL dose, after intraperitoneal or oral administration of HAL, 4 or 8h after its injection, using red or green light, after protection of the liver or cooling of the abdominal wall. Toxicity was assessed by blood tests quantifying hematocrit, liver and muscular enzymes and by pathological examination of abdominal and intrathoracic organs after treatment. The results were analyzed in the light of quantification of fluorescence and protoporphyrin IX (PPIX) content of the same organs. RESULTS: PDT with HAL induced rhabdomyolysis, intestinal necrosis and liver function test anomalies, leading to death in 2 out of 34 rats. The liver and the intestine contained high levels of PPIX (3-5 times more than tumor nodules). CONCLUSION:HAL PDT lacked specificity. However, the strategy associating diagnosis, treatment and evaluation of the results in one single procedure was effective and should be tested with other photosensitizers.