Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model.
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.
Hornung
R
R
Beckman Laser Institute and Medical Clinic, University of California, Irvine, USA. renehornung@clinch.ch
Fehr
M K
MK
Monti-Frayne
J
J
Krasieva
T B
TB
Tromberg
B J
BJ
Berns
M W
MW
Tadir
Y
Y
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin