Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model.

Abstract

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-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(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 (+/- 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.

• Authors: R Hornung, M K Fehr, J Monti-Frayne, T B Krasieva, B J Tromberg, M W Berns, Y Tadir
• Journal: Photochemistry and photobiology (Photochem Photobiol) Vol. 70 Issue 4 Pg. 624-9 (Oct 1999) ISSN: 0031-8655 [Print] United States
• PMID: 10546556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Mesoporphyrins
• Photosensitizing Agents
• Polyethylene Glycols
• temoporfin

Topics

• Animals
• Disease Models, Animal
• Female
• Mesoporphyrins (administration & dosage, pharmacokinetics)
• Ovarian Neoplasms (drug therapy, pathology)
• Photochemotherapy
• Photosensitizing Agents (administration & dosage, pharmacokinetics)
• Polyethylene Glycols (administration & dosage)
• Rats
• Rats, Inbred F344