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doi:10.1016/S1095-6433(01)00545-1    
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Copyright © 2002 Elsevier Science Inc. All rights reserved.

Tumor PImage 2 changes during photodynamic therapy depend upon photosensitizer type and time after injection*1

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Brian W. PogueCorresponding Author Contact Information, E-mail The Corresponding Author, a, Julia A. O'Harab, Isak A. Goodwina, Carmen J. Wilmotb, Gregory P. Fourniera, Altug R. Akaya and Harold Swartzb

a Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA

b Department of Radiology, Dartmouth Medical School, Hanover, NH 03755, USA


Received 10 January 2001; 
revised 16 March 2001; 
accepted 19 March 2001. 
Available online 24 January 2002.

Abstract

In this study, the vascular and tissue oxygen changes induced by photodynamic therapy in the RIF-1 tumor were examined, using electron paramagnetic resonance (EPR) oximetry. Two photosensitizers, including verteporfin (BPD-MA in a lipid-based formulation) and aminolevulinic acid-induced protoporphyrin IX (ALA-PPIX), were investigated with optical irradiation, sufficient to induce sub-curative damage in the tumor tissue, and the transient changes in PImage 2 and vascular perfusion were examined. A large increase in tissue oxygenation (from 3 up to 9.5 mmHg) was observed when treated with ALA-PPIX based photodynamic therapy, which lasted during the treatment and a small residual increase that returned back to baseline levels by 48 h after treatment. With verteporfin-based photodynamic therapy, one group of animals was irradiated 15 min after injection and exhibited a small decrease in oxygenation relative to pre-irradiation levels. The second group was irradiated at 3 h after injection and exhibited a large increase in the average PImage 2, (from 3 to 15 mmHg) by the end of the treatment. These observations indicate that photodynamic therapy significantly increases tissue PImage 2 under certain treatment conditions, with the potential cause being either increased local blood flow or decreased local oxygen metabolic consumption due to cellular damage.

Author Keywords: Photodynamic; EPR; Benzoporphyrin derivative; PImage 2; Oxygen; Photochemotherapy; RIF-1 tumor; Singlet oxygen

Article Outline

1. Introduction
2. Materials and methods
2.1. Photosensitizer
2.2. Tumor model
2.3. Light delivery
2.4. Tumor PImage 2 measurement
2.5. Chemical extraction
3. Results
3.1. In vivo oxygen measurements during and after PDT
3.2. Photosensitizer concentration in vivo
4. Discussion
Acknowledgements
References




*1 This paper was presented as part of ISOTT2000 held in Nijmegen, The Netherlands, August 20–25, 2000. Organizer was Dr Berend Oeseburg.

Corresponding Author Contact Information Corresponding author. Tel.: +1-603-646-3861; fax: +1-603-646-3856; email: pogue@dartmouth.edu


 
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