Fractionated illumination for oesophageal ALA-PDT: Effect on blood flow and PpIX formation

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.