title: Localization and efficacy analysis of the phototherapeutic lutetium texaphyrin (PCI-0123) in the murine EMT6 sarcoma model.
abstract: Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light. The sensitizer is highly fluorescent and exhibits a strong, broad emission signal at 750 nm. In vitro cellular uptake studies revealed an increase in sensitizer retention with incubation time. Confocal laser scanning microscopy demonstrated that the intracellular localization site of PCI-0123 is the lysosomes. Ensuing illumination of the EMT6 cells led to lysosomal breakup, extensive cytoplasmic blebbing and subsequent cell death. Noninvasive spectral imaging analysis of PCI-0123 fluorescence depicted selective drug uptake, compared to surrounding normal tissue, in EMT6 mammary sarcomas syngeneic to BALB/c mice. The PCI-0123 PDT was shown to effectively treat the EMT6 murine sarcoma. Irradiation (732 nm light) 3 h postintravenous injection of 10 mumol PCI-0123 per kg gave 100% cures (no evidence of cancer), whereas light exposure at 5 h resulted in 75% cures. Hematoxylin and eosin histologic examination of photoirradiated tumors indicated apoptosis of the EMT6 neoplasms at early times post-PDT progressing, with time, to extensive necrotic areas. Gel electrophoresis of extracted photoirradiated tumors showed the typical apoptotic DNA ladder pattern that increased in intensity following PDT treatment.
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, CA 94086, USA. Kathy@pcyc.com
authors.forename: K W
authors.initials: KW
authors.lastname: Woodburn
authors.forename: Q
authors.initials: Q
authors.lastname: Fan
authors.forename: D R
authors.initials: DR
authors.lastname: Miles
authors.forename: D
authors.initials: D
authors.lastname: Kessel
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: S W
authors.initials: SW
authors.lastname: Young
mesh_terms: D000818:Animals; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008665:Metalloporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D018613:Microscopy, Confocal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium; C437683:motexafin gadolinium