title: Photodynamic therapy in retinoblastoma: effects of verteporfin on retinoblastoma cell lines.
abstract: OBJECTIVE
  In contrast to the excellent survival rates of the malignant childhood tumor retinoblastoma (RB), morbidity is high in patients with this disease because of the enucleation or loss of retinal areas caused by current bulb-saving therapies. The authors aimed to preclinically assess the effects of photochemotherapy using second-generation photochemotherapeutics as a prerequisite to develop a promising therapeutic alternative. This therapy implies intravenous application of a photosensitizer activated locally by light of the appropriate wavelength. Activation leads to the formation of free radicals, vascular occlusion, and death of affected cells in the area of irradiation. The photosensitizer verteporfin is approved for the therapy of neovascularizations, such as age-related maculopathy.
  
  
  METHODS
  The uptake of verteporfin in RB cell lines was investigated. Established RB cell lines, an RB subline resistant to etoposide, and dissociated cells from a primary RB were incubated with verteporfin and irradiated with activating laser light. Proliferation was measured at different time points after application.
  
  
  RESULTS
  All five RB cell lines investigated incorporated verteporfin, and nanomolar concentrations were sufficient for effective killing. At lower doses, surviving cells started to proliferate again after several days, but verteporfin 50 ng/mL and 100 J/cm(2) were sufficient for irreversible killing. High verteporfin concentrations caused cell death with little to no irradiation. Etoposide-resistant cells and primary tumor cells had a comparable susceptibility to photodynamic therapy (PDT) as established parental cell lines.
  
  
  CONCLUSIONS
  PDT using verteporfin efficiently kills chemotherapy-resistant and nonresistant retinoblastoma cell lines and primary tumor cells in vitro, and it warrants further preclinical evaluation as a therapeutic option for the treatment of retinoblastoma.
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital, Essen, Germany. harald.stephan@uni-due.de
authors.forename: Harald
authors.initials: H
authors.lastname: Stephan
authors.forename: Réka
authors.initials: R
authors.lastname: Boeloeni
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Norbert
authors.initials: N
authors.lastname: Bornfeld
authors.forename: Andreas
authors.initials: A
authors.lastname: Schueler
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D009994:Osmolar Concentration; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D011166:Porphyrins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012175:Retinoblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000077362:Verteporfin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D005047:Etoposide