title: Cellular and antitumor activity of a new diethylene glycol benzoporphyrin derivative (lemuteporfin).
abstract: A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure to activating light. The cellular uptake of lemuteporfin was rapid, with maximum levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more of the lemuteporfin than their quiescent equivalents, supporting selectivity. Photosensitizer fluorescence in the skin increased rapidly within the first few minutes following intravenous administration to mice, then decreased over the next 24 h. Skin photosensitivity reactions indicated rapid clearance of the photosensitizer. Intravenous doses as low as 1.4 micromol/kg combined with exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In conclusion, this new benzoporphyrin was found to be an effective photosensitizer, showing rapid uptake and clearance both in vitro and in vivo. This rapid photosensitization of tumors could be useful in therapies requiring a potent, rapidly accumulating photosensitizer, while minimizing the potential for skin photosensitivity reactions to sunlight following treatment.
authors.affiliation: QLT Inc., 887 Great Northern Way, Vancouver, BC, Canada, V5T 4T5. rboch@qltinc.com
authors.forename: Ron
authors.initials: R
authors.lastname: Boch
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Canaan
authors.forename: Angela
authors.initials: A
authors.lastname: Cho
authors.forename: David D
authors.initials: DD
authors.lastname: Dolphin
authors.forename: Lina
authors.initials: L
authors.lastname: Hong
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Jain
authors.forename: John R
authors.initials: JR
authors.lastname: North
authors.forename: Anna M
authors.initials: AM
authors.lastname: Richter
authors.forename: Claire
authors.initials: C
authors.lastname: Smits
authors.forename: Ethan D
authors.initials: ED
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D005026:Ethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D006415:Hematoporphyrins; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry* / Q000633:toxicity; D013053:Spectrophotometry
chemical_list: D000970:Antineoplastic Agents; D005026:Ethylene Glycols; D006415:Hematoporphyrins; D011166:Porphyrins; C013484:diethylene glycol; C510896:lemuteporfin