J. Van Den Boogert et al., Fractionated illumination for oesophageal ALA-PDT: Effect on blood flow and PpIX formation, LASER MED S, 16(1), 2001, pp. 16-25
The effect of fractionating the 633 nm illumination of 5-aminolaevulinic (A
LA)-based photodynamic therapy (PDT) of the normal rat oesophagus was studi
ed. Fractionation of the illumination could enhance the PDT effect in two w
ays: (a) delay of the vascular shutdown or relaxation of the vasoconstricti
on induced by ALA-PDT and (b) use of newly formed protoporphyrin TX (PpIX),
produced during the dark interval. Forty rats were randomly allocated to t
wo groups of 20 animal each. To study vascular effects, in group 1 illumina
tion with 633 nm (100 mW/cm) was performed at 3 h after oral ALA administra
tion (200 mg/kg) either continuously with 20 J/cm diffuser length (n=5) or
fractionated 2 x 10 J/cm with a 150 s interval (n=5), five animals served a
s controls. Flood flow was measured with a laser Doppler flowmeter. To stud
y the effect of renewed PpIX forming, animals in group 2 were illuminated c
ontinuously at 3 h after ALA with 20 J/cm (n=5) or 40 J/cm (n=5) or fractio
nated 2 x 20 J/cm with a 3 h interval (n=5), five animals served as control
s. In all animals the in vivo fluence rate and PpIX fluorescence were measu
red during illuminations and animals were killed at 48 h after PDT.
ALA-PDT did not cause any significant vasoconstriction. Fluorescence measur
ements and dosimetric results in group 1 did not differ between animals ill
uminated continuously or fractionated with a 150 s interval. In group 2, du
ring a 3 h dark interval, PpIX fluorescence increased and was bleached duri
ng the second illumination. The tissue optical properties changed during th
e 3 h dark interval, resulting in a lower in vivo fluence rate (p less than
or equal to 0.001). Fractionation did not result in more oesophageal damag
e. It was concluded that a 150 s interval during illumination in ALA-PDT do
es not increase oesophageal blood flow. During an interval of 3 h new PpIX
is formed. In the present study, fractionated illumination using short or l
ong time intervals did not result in more damage. Thus, this study shows no
evidence for improved PDT effect with fractionated light delivery.