Light delivery over extended time periods enhances the effectiveness of photodynamic therapy.
OBJECTIVE
The rate of energy delivery is a principal factor determining the biological consequences of photodynamic therapy (PDT). In contrast to conventional high-irradiance treatments, recent preclinical and clinical studies have focused on low-irradiance schemes. The objective of this study was to investigate the relationship between irradiance, photosensitizer dose, and PDT dose with regard to treatment outcome and tumor oxygenation in a rat tumor model.


METHODS
Using the photosensitizer HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide), a wide range of PDT doses that included clinically relevant photosensitizer concentrations was evaluated. Magnetic resonance imaging and oxygen tension measurements were done along with the Evans blue exclusion assay to assess vascular response, oxygenation status, and tumor necrosis.


RESULTS
In contrast to high-incident laser power (150 mW), low-power regimens (7 mW) yielded effective tumor destruction. This was largely independent of PDT dose (drug-light product), with up to 30-fold differences in photosensitizer dose and 15-fold differences in drug-light product. For all drug-light products, the duration of light treatment positively influenced tumor response. Regimens using treatment times of 120 to 240 min showed marked reduction in signal intensity in T2-weighted magnetic resonance images at both low (0.1 mg/kg) and high (3 mg/kg) drug doses compared with short-duration (6-11 min) regimens. Significantly greater reductions in pO(2) were observed with extended exposures, which persisted after completion of treatment.


CONCLUSIONS
These results confirm the benefit of prolonged light exposure, identify vascular response as a major contributor, and suggest that duration of light treatment (time) may be an important new treatment variable.
Seshadri
Mukund
M
Department of Cell Stress Biology and Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Bellnier
David A
DA
Vaughan
Lurine A
LA
Spernyak
Joseph A
JA
Mazurchuk
Richard
R
Foster
Thomas H
TH
Henderson
Barbara W
BW
D000818:Animals; D015687:Cell Hypoxia; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D008027:Light; D010100:Oxygen / Q000032:analysis; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome
D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D010100:Oxygen