title: A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells.
abstract: Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.
authors.affiliation: Surgery Department, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: M
authors.initials: M
authors.lastname: Tolentino
authors.forename: T
authors.initials: T
authors.lastname: Okunaka
authors.forename: M L
authors.initials: ML
authors.lastname: Eckhauser
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: F
authors.initials: F
authors.lastname: Valencic
authors.forename: J D
authors.initials: JD
authors.lastname: Fleischmann
authors.forename: M M
authors.initials: MM
authors.lastname: Sarasua
authors.forename: K A
authors.initials: KA
authors.lastname: Koehler
mesh_terms: D006801:Humans; D008954:Models, Biological; D010713:Phosphatidylcholines; D010778:Photochemotherapy / Q000295:instrumentation*; D011524:Protoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D010713:Phosphatidylcholines; D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C075275:PH 1008