title: Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor.
abstract: In the present study, the effects of photodynamic therapy (PDT) with verteporfin on tumor blood flow and tumor regrowth were compared as verteporfin distributed in different compartments within the RIF-1 tumor. Tissue distribution of verteporfin was examined by fluorescence microscopy, and blood flow measurements were taken with a laser Doppler system. It was found that, at 15 min after drug administration, when verteporfin was mainly confined within the vasculature, PDT induced a complete arrest of blood flow by 6 h after treatment. PDT treatment at a longer drug-light interval (3 h), which allowed the drug to diffuse to the tumor interstitium, caused significantly less flow decrease, only to 50% of the initial flow in 6 h. A histological study and Hoechst 33342 staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors treated with 15-min interval PDT was 64% of that of the control group. However, when tumors were treated with 3-h interval PDT, the regrowth rate was not significantly different from that of the control, indicating that only the 15-min interval PDT caused serious damage to the tumor vascular bed. These results support the hypothesis that temporal pharmacokinetic changes in the distribution of the photosensitizer between the tumor parenchyma and blood vessels can significantly alter the tumor target of PDT.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.forename: Isak A
authors.initials: IA
authors.lastname: Goodwin
authors.forename: Julia A
authors.initials: JA
authors.lastname: O'Hara
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Wilmot
authors.forename: John E
authors.initials: JE
authors.lastname: Hutchins
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000528:radiation effects; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D016896:Treatment Outcome; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin