Timing of illumination is essential for effective and safe photodynamic therapy: a study in the normal rat oesophagus

5-Aminolaevutinic acid (ALA)-induced, protoporphyrin IX (Pp[X)-mediated pho todynamic therapy (PDT) is an experimental treatment modality for (pre)mali gnant oesophageal lesions. This study aimed to optimize the time of illumin ation after ALA administration. Six groups of eight rats received 200 mg kg (-1) ALA orally, eight rats served as controls. illumination was performed at 1, 2, 3, 4, 6 or 12 h after ALA administration with a 1-cm cylindrical d iffuser placed in a balloon catheter (laser parameters: 633 nm, 25 J radian t energy, power output 100 mW). During illumination, fluorescence measureme nts and light dosimetry were performed. Animals were sacrificed at 48 h (n = 4) or 28 days (n = 4) after PDT. At day 28, an oesophagogram was performe d. Largest PpIX fluorescence was found at 3 h after ALA administration. In vivo fluence rate was three times higher than the calculated incident fluen ce rate. At 48 h after PDT major epithelial damage was found in all animals illuminated at 2 h, whereas less epithelial damage was found at 3-6 h and none at 1 and 12 h. In animals illuminated at 4, 6 and 12 h, but not at 2 h , oesophagograms showed severe dilatations and histology showed loss of Sch wann cells. These results demonstrate that the choice of time interval betw een ALA administration and illumination is critical for achieving epithelia l damage without oesophageal functional impairment. A short interval of 2-3 h seems to be most appropriate.