Vergleichende Wirkstudie zu Hypericin und 131I-Hypericin bei der photodynamischen Therapie des kindlichen Rhabdomyosarkoms

Rhabdomyosarkome gehören zu den häufigsten soliden Tumoren des Kindesalters. Besonders der alveoläre Subtyp zeigt ein invasives Wachstum mit frühzeitiger Metastasierung. Trotz intensiver Therapiestrategien, bestehend aus system- und lokaltherapeutischen Maßnahmen, bleibt die Prognose oftmals deutlic...

Full description

Saved in:
Bibliographic Details
Main Author: Ocker, Lennart Tim
Contributors: Seitz, Guido (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2020
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!

Rhabdomyosarcomas are the most common malignant soft tissue tumors in pediatric patients. Specifically, the alveolar subtype shows local infiltration and early systemic metastasis. Despite intensive therapeutic strategies including mutilating surgery, systemic and radiation therapy, the prognosis of this tumor entity remains still poor. As a consequence, there is an urgent need for new innovations in the therapy of soft tissue cancer. Hypericin, a major compound of St. John ́s wort, shows photosensitizing properties and has been clinically established for photodynamic therapy of various malignancies. In this study, hypericin was employed for in vitro photodynamic treatment of different alveolar RMS cell lines and showed strong anti-tumor efficiency at low concentrations. The different tumor cell lines showed individual intracellular distributions, as hypericin led to selective disintegration of cellular compartments. Apoptosis could be identified as the predominant cellular death-mode. For the first time, cytomorphological transformations after PDT could be observed at an electron-microscopical level and indicated a disruption of the cell membrane. As light only permeates the superficial layers of a three-dimensional tumor, the impact of PDT remains restricted at the tumor ́s surface. Via coupling of radioactive 131I at the hypericin-molecule, the range of action of this therapy could be amplified, as deeper tumor layers would be reached by a targeted radiotherapy. Non-radioactive iodination of hypericin was performed easily and cost-efficient and led to a slight attenuation of its anti-tumor properties. 131I-hypericin showed strong tumoricidal efficiency in rhabdomyosarcoma cells at doses of 10.000 and 100.000 Bq, however additional photodynamic treatment did not lead to an enhancement of cytotoxicity due to low hypericin-concentrations. Furthermore, a combinational treatment including systemic targeted 131I-Hypericin radiotherapy and standard Hypericin-PDT seems promising for clinical tumor-therapy. Further in vivo studies on this topic are scheduled by our pediatric surgery research team.