title: Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer.
abstract: An improved formulation of the photosensitizer chlorin e6 (Ce6) in combination with the hydrophilic polymer polyvinylpyrrolidone (PVP) was investigated for its potential clinical applications in fluorescence diagnosis and photodynamic therapy (PDT) of cancer. This study reports the comparative preclinical biodistribution and efficacy of Ce6 delivered with or without PVP versus dimethyl sulfoxide (DMSO). The safety and fluorescence pharmacokinetics of Ce6-PVP in humans was also accessed. Biodistribution results showed that Ce6-PVP had higher tumor to normal tissue ratio compared to the other formulations. The sensitivity and specificity derived from the area under the receiver operating characteristics curves showed that the formulations were able to discriminate tumor from peritumoral muscle in the following order: Ce6-PVP > Ce6 > Ce6-DMSO. In vitro PDT results showed that Ce6-PVP was found to induce selective phototoxicity in leukemic cells compared to peripheral mononuclear blood cells. In addition, in vivo light irradiation at 1h after Ce6-PVP was found to induce greater tumor necrosis without causing animal toxicity. In patients, preferential accumulation of Ce6-PVP was observed in angiosarcoma lesions compared to normal skin following intravenous administration. In conclusion, PVP significantly enhanced the Ce6 concentration in tumors compared with Ce6 alone and increased the therapeutic index of PDT without any side effects in animal model. No serious adverse events were observed in human as well.
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, Singapore.
authors.forename: William Wei Lim
authors.initials: WW
authors.lastname: Chin
authors.forename: Paul Wan Sia
authors.initials: PW
authors.lastname: Heng
authors.forename: Patricia Soo Ping
authors.initials: PS
authors.lastname: Thong
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Bhuvaneswari
authors.forename: Werner
authors.initials: W
authors.lastname: Hirt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kuenzel
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002735:Chlorophyllides; D006394:Hemangiosarcoma / Q000473:pathology / Q000628:therapy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017711:Nonlinear Dynamics; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D011166:Porphyrins / Q000008:administration & dosage* / Q000627:therapeutic use*; D011205:Povidone / Q000737:chemistry; D012372:ROC Curve; D012044:Regression Analysis; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D011205:Povidone