The effect of fluence rate on the acute response of vessel diameter and red blood cell velocity during topical 5-aminolevulinic acid photodynamic therapy.
BACKGROUND
In a previous study it is shown that for topically applied ALA-PDT, PpIX concentration correlates with vascular changes including vasoconstriction and/or vascular leakage of small vessels and arterioles in the mouse epidermis and dermis. In this study we report on vascular responses induced by ALA-PDT for different fluence rates, including both changes in vessel diameter and dynamics in RBC velocity in arterioles, imaged using intra-vital confocal microscopy in skinfold chambers in hairless mice. Our interest is in the dynamics of vascular changes in the early stages of illumination.


METHODS
We have determined the total PDT dose to be relatively low, 13 J cm(-2), and fluence rates of 26, 65 and 130 mW cm(-2) were investigated. Local vascular effects occurred very soon after the start of the therapeutic illumination in ALA-PDT.


RESULTS
In this study, we did not find a significant difference between fluence rates. Arterioles were particularly sensitive to vasoconstriction during low dose PDT, often resulting in complete vasoconstriction. When we observed complete vasoconstriction, this coincided with changes in RBC velocity.


CONCLUSIONS
Since the therapeutic effects of PDT are dependent on a fine balance between the need for oxygen during illumination and disruption of the vasculature, the results of the present study add to our understanding of acute vascular effects during ALA-PDT and aid our efforts to optimize PDT using porphyrin pre-cursors.
Department of Radiation Oncology, Center for Optical Diagnostics and Therapy, Postgraduate School Molecular Medicine, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
F
F
van Leeuwen-van Zaane
Department of Otolaryngology - Head and Neck Surgery, Erasmus MC, Rotterdam, The Netherlands.
H S
HS
de Bruijn
Department of Radiation Oncology, Center for Optical Diagnostics and Therapy, Postgraduate School Molecular Medicine, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
A
A
van der Ploeg-van den Heuvel
Department of Radiation Oncology, Center for Optical Diagnostics and Therapy, Postgraduate School Molecular Medicine, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
H J M C
HJ
Sterenborg
Department of Otolaryngology - Head and Neck Surgery, Erasmus MC, Rotterdam, The Netherlands. Electronic address: d.robinson@erasmusmc.nl.
D J
DJ
Robinson
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D011524:Protoporphyrins / Q000378:metabolism*; D011829:Radiation Dosage; D012867:Skin / Q000098:blood supply / Q000528:radiation effects; D014661:Vasoconstriction / Q000502:physiology* / Q000528:radiation effects
D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
5-Aminolevulinc acid; Flow; Intra-vital microscopy; Red blood cell velocity; Vascular response; Vessel diameter