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Proceedings Paper

PD and PDT for hepatoblastoma? Preclinical considerations
Author(s): Herbert Stepp; Florian Bergmann; Ann Johansson; Michael Heide; Roman Metzger; Udo Rolle; Holger Till
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Paper Abstract

Objective: Provide preclinical data on the feasibility of 5-aminolevulinic acid (5-ALA) -based photodetection (PD) and Photodynamic Therapy (PDT) of early childhood tumors. Methods: Hepatoblastoma (HuH6), neuroblastoma (MHH-NB11) and N1-fibroblast cell lines were tested for their relative capacities to synthesize Protoporphyrin IX (PpIX) from 5-ALA and for their susceptibility to PDT in vitro. HuH6-cells were also inoculated in the peritoneum of rats. The pharmacokinetics of porphyrin accumulation was measured in 9 rats by laparoscopic spectroscopy. 5-ALA was applied by i.p. injection of 500 mg/kg bw. In another 21 animals, tumors (n=20), liver (n=5) and peritoneum (n=4) were treated by PDT laparoscopically. 48 h after irradiation, animals were again incubated with 5-ALA and then sacrificed and tissues were removed for further investigation. Results: Both tumor cell lines showed higher levels of porphyrin fluorescence than the fibroblasts. Cell viability testing proved the HuH6 cells to be most susceptible to PDT. Pharmacokinetic measurements of PpIX in xenografted tumors showed a peak at 80-200 min after i.p. injection of 5-ALA. Irradiation resulted in pronounced photobleaching at all irradiated sites and necrosis of tumor and liver tissue, whereas peritoneum appeared to remain unaffected. Necrosis induced by PDT could be seen in fluorescence microscopy due to the lack of porphyrin synthesis in necrotic tissue after the re-incubation with 5-ALA.

Paper Details

Date Published: 7 June 2011
PDF: 9 pages
Proc. SPIE 8092, Medical Laser Applications and Laser-Tissue Interactions V, 80920I (7 June 2011); doi: 10.1117/12.889860
Show Author Affiliations
Herbert Stepp, Klinikum der Univ. München (Germany)
Florian Bergmann, Klinikum der Univ. München (Germany)
Ann Johansson, Klinikum der Univ. München (Germany)
Michael Heide, Klinikum der Univ. München (Germany)
Roman Metzger, Univ. of Leipzig (Germany)
Udo Rolle, Univ. of Leipzig (Germany)
Holger Till, Univ. of Leipzig (Germany)

Published in SPIE Proceedings Vol. 8092:
Medical Laser Applications and Laser-Tissue Interactions V
Ronald Sroka; Lothar D. Lilge, Editor(s)

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