Premium
Highly Selective Targeting of Ovarian Cancer with the Photosensitizer PEG‐m‐THPC in a Rat Model
Author(s) -
Hornung Rene,
Fehr Mathias K.,
MontiFrayne Jill,
Krasieva Tatiana B.,
Tromberg Bruce J.,
Berns Michael W.,
Tadir Yona
Publication year - 1999
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1999.tb08261.x
Subject(s) - photosensitizer , ovarian cancer , photodynamic therapy , debulking , peg ratio , medicine , pharmacokinetics , in vivo , cancer , ovary , cancer research , chemistry , pathology , pharmacology , biology , photochemistry , microbiology and biotechnology , organic chemistry , finance , economics
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.