title: Lutetium texaphyrin (PCI-0123): a near-infrared, water-soluble photosensitizer.
abstract: Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and 14C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 mumol/kg with irradiation 5 h postinjection at 150 J/cm2 and 150 mW/cm2, had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 +/- 14 mm3) and also had significant efficacy (P < 0.0001) in treating larger neoplasms (147 +/- 68 mm3). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 mumol/kg and 150 J/cm2 at 150 mW/cm2. The PDT efficacy was attributable to the selective uptake/retention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.
authors.affiliation: Pharmacyclics, Inc., Sunnyvale, CA 94086, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Young
authors.forename: K W
authors.initials: KW
authors.lastname: Woodburn
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: T D
authors.initials: TD
authors.lastname: Mody
authors.forename: Q
authors.initials: Q
authors.lastname: Fan
authors.forename: J L
authors.initials: JL
authors.lastname: Sessler
authors.forename: W C
authors.initials: WC
authors.lastname: Dow
authors.forename: R A
authors.initials: RA
authors.lastname: Miller
mesh_terms: D000818:Animals; D005260:Female; D007259:Infrared Rays; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014867:Water
chemical_list: D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D014867:Water; C102825:motexafin lutetium; C437683:motexafin gadolinium