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Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model
Wissenschaftlicher Artikel/Review - 01.06.1999
Hornung René, Fehr M.K., Monti-Frayne J., Tromberg T.B., Krasieva J., Berns B.J., Tadir Y.
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Photodynamic therapy (PDT) uses light to activate a photosensitizer that has been absorbed or retained preferentially by cancer cells after systemic administration. The first pegylated photosensitizer, tetrakis-(m-methoxypo-lyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-te-trakis(3-hydroxyphenyl)-21,23-[H]-porphyrin (PEG-m-THPC), was evaluated to target selectively unresectable pelvic ovarian cancer bulks. Our goals were two-fold: (1) to establish an ovarian cancer model suitable for the development of debulking techniques and (2) to characterize the pharmacokinetics and tumor selectivity of PEG-m-THPC by fluorescence microscopy. NuTu-19 ovarian cancer cells were injected into the caudal part of the right psoas muscle of Fisher rats. Five weeks later, 30 mg/kg body weight of PEG-m-THPC was injected intravenously. Necropsy was performed between 4 and 10 days following drug application, and fluorescence of the tumor and various abdominal organs was measured. All rats developed bulky pelvic tumors with an average diameter of 2.6 cm (± 0.6 SD). Tumor masses were encompassing and infiltrating pelvic organs in a similar manner to ovarian cancers in humans. Fluorescence of cancer tissue was maximal 8–10 days following drug application. At 8 days, the tumor-to-tissue ratio was 40:1 (plusmn; 12 SE) for most abdominal organs. We conclude that this tumor model may be used for the study of new pelvic debulking techniques, and that the tumor selectivity of PEG-m-THPC is exceptionally high 8 days after drug application. Based on these data, we are currently developing a PDT-based minimally invasive debulking technique for advanced ovarian cancer.